Tag Archives: Paediatrics

Genetically speaking

Genetic testing has grown from a niche speciality for rare disorders to a broad scope of applications for routine, complex diseases to its use in personalised health solutions and precision medicine. There is a need for healthcare providers, the diagnostic community and the government to step-up and uplift genetic diagnostics, making it available, accessible and safe for all.

The article was published in the magazine of The Sunday Standard and
The New Indian Express in the edition dated March 21, 2021.
https://www.newindianexpress.com/lifestyle/health/2021/mar/21/the-anatomy-of-a-gene-2278437.html

Dr G. Arun Kumar, Scientific Affairs Manager, MedGenome Labs

Dr G. Arun Kumar, Scientific Affairs Manager, MedGenome Labs.

Explain genetic testing/screening to a layman. What are the challenges of genetic testing?

To understand genetic testing, it is essential to understand the role of DNA and genes in our bodies. We can see our genome as the instruction book in our body which exists in multiple volumes, the genes as the individual pages present in these books, while the DNA is the language in which the pages are written. Genes regulate specific parts or functions of a cell. We inherit two copies of every gene, one from each parent. Sometimes multiple genes are required to control one function. Other times, just one gene may influence multiple functions. The DNA sequence of a gene is the code that instructs the cell to make proteins. These proteins, in turn, affect all bodily functions. Any variations in the DNA sequence can disrupt the protein it encodes and put us at greater risk of acquiring certain diseases in our lives. Genetic testing is a tool used to look at our DNA to detect such variants. Results from a genetic test can significantly help doctors understand the cause of a disease or symptoms, predict an individual’s risk of developing certain diseases, tell if one could pass the disease to their children and help in choosing the best treatment that can be tailored for the individual. For instance, if a person has cancer, then a genetic test can tell if the person inherited a cancer-causing genetic aberration. Early detection can also help doctors make an informed decision about the same and tell if the patient is at risk of developing any other type of cancers as well. Genetic testing of cancer tissue can help in identifying genetic variants that can be targeted using specific drugs.

 Performing genetic testing requires high expertise both in terms of laboratory testing and analysis of genetic data. Understanding a genetic testing report for a commoner requires a clinician or a genetic counsellor.

If I have hereditary spherocytosis, can I get to know the chances of it being carried by my offspring and how?

In most cases, spherocytosis occurs as an inherited disease that changes and reduces the life of red blood cells in the patient’s body and causes anaemia. The initial evaluation of hereditary Spherocytosis involves a physical inspection, a review of the family history, and few lab tests on blood samples. In Spherocytosis, the structure of red blood cell changes, attributable to a defective protein produced in the cell due to genetic mutations. Genetic testing for spherocytosis looks for variants in the genes ANK1, EPB42, SLC4A1, SPTA1, SPTB. Some of these genetic variants are inherited in an “Autosomal recessive” manner. It means that for a person to express the disease (s)he must inherit genetic variants in both the gene’s copies. If a person has inherited a genetic variant in only one copy of the gene, the other copy being healthy, then this person is termed as a carrier. A person with the disease will 100% pass on one defective copy of the gene to the offspring. On the other hand, an individual who is a carrier has a 50% chance of passing the offspring’s variant. In either case, if the partner of the individual also passes on one defective copy to the offspring, then the child will develop the disease.

What are the things to keep in mind while opting for genetic testing/screening? What are its hope for medical science in the days to come?

Genetic testing can help in identifying an inherited disease risk in an individual. It is important to discuss the reasons for a genetic test with your doctor as they may guide you to a medical geneticist who is trained to diagnose a genetic condition, select the appropriate genetic tests, explain the test results, and recommend personalized treatment and prevention options. Before opting for genetic testing, one should gather as much information as possible about the family’s medical history to understand the risk better.

What are the diseases for which this screening works?

MedGenome currently offers more than 475 genetic tests across several disease categories such as paediatrics, neurology, oncology, haematology, endocrinology, nephrology, ophthalmology, etc. Any disorder that has an established genetic basis can be screened. Additionally, we also offer carrier screening for couples that will tell the carrier status of various genetic variants in the couple. This shall aid the clinician counsel the couple for future pregnancy.

What are the services offered by MedGenome?

Medgenome offers genetic testing services under four major divisions, viz – Actia, Claria, Prima and Micra. The Actia division deals with genetic testing of all inherited disorders encompassing all major medicine disciplines, including neurology, ophthalmology, cardio-vascular, Metabolic disorder, Nephrology, etc. The Claria division deals with reproductive genetics that offers various prenatal genetic testing panels, NIPT, and pre-implementation genetic testing. The Prima division deals with Oncology (solid tumours and Leukaemia) and Hematology range of testing. All these tests are College of American Pathology accredited. The Micra division is a new addition to our portfolio that is involved in infectious disease testing. In this range, we have indigenously developed the first whole genome sequencing of Mycobacterium tuberculosis directly from a patient’s sputum.

MedGenome is the market leader in India’s genetic diagnostics and is one of the largest high- throughput NGS sequencing labs in South Asia. We possess state-of-the-art Next-generation Sequencing (NGS) facility, which houses cutting-edge genome sequencing platforms such as Illumina’s NovaSeq, HiSeq X, HiSeq 4000 and 2500, MiSeq, etc. A sophisticated IHC pathology lab supports our Sequencing facility. We also offer other genomic testing technologies such as FISH, PCR, Sanger Sequencing, and Microarray to offer comprehensive diagnostic solutions to clinicians, hospitals and researchers. We offer genetic testing at different scales such as identification of point mutations using Sanger technique, RT-PCR; chromosomal level aberrations using FISH, Chromosomal microarray; multigene and whole-genome sequencing using Next Generation Sequencing

Is genetic testing gaining popularity?

Genetic testing is gaining popularity among all medicine disciplines because of its wide applications inpatient management and family planning. Almost all significant guidelines of different medical disciplines have incorporated genetic testing in their statements. The awareness of genetic testing among the general public is also increasing so much so that direct consumer testing for personal genomics is not far from reality.

What are the cost implications?

Genome sequencing technology has undergone tectonic changes in the last decade. The development of superior technology and informatics tools has improved genome sequencing precision and has contributed to a 100-fold reduction in sequencing cost. MedGenome has been a forerunner in India for democratising genome sequencing by making it affordable, beyond the reach of a commoner a decade ago, without compromising the quality. 

Arun Kiran P,  Lead Genetic Counsellor, Prenetics Limited

Arun Kiran P,  Lead Genetic Counsellor, Prenetics Limited.

Explain genetic testing?

Genetic testing, also known as DNA testing, is a process of identifying changes in chromosomes, genes, or proteins.

Genetic testing results can help individuals either confirm or rule out the possibility of having a clinical condition; identifying genetic mutations can determine a person’s chance of developing genetic predisposition risk or passing on a genetic disorder.

There are several genetic tests in the market, and the purpose of these tests solely depends on the case and the scenario it is in use. Several methods are used for genetic testing:

  • Molecular genetic tests: where single genes or short lengths of the DNA variations are identified that can lead to a genetic disorder. With the recent advancements in the genetic testing space, platforms like the Next Generation Sequencing allow individuals to access Whole Genome or Exome Sequencing (WES).

One’s DNA is composed of more than 3 billion base pairs. Collectively, these pairs are called the genome. A portion of the genome is called the exome, the protein-sequencing region of one’s DNA.

  • Chromosomal genetic tests analyse whole chromosomes or long lengths of DNA to see if there are large genetic changes, such as an extra copy of a chromosome, that cause a genetic condition.
  • Biochemical genetic tests study the amount or activity level of proteins; abnormalities in either can indicate changes to the DNA that result in a genetic disorder.

2) If I have hereditary spherocytosis, can I get to know the chances of it being carried by my offspring and how?

Hereditary spherocytosis is a condition characterized by haemolytic anaemia (when red blood cells are destroyed earlier than normal).

Signs and symptoms can range from mild to severe and may include anaemia, pale skin, fatigue, jaundice, gallstones, and/or enlargement of the spleen. Severe cases involve short stature, delayed puberty and skeletal abnormalities.

Mutations cause this condition in any of the several genes, such as the ANK1, EPB42, SLC4A1, SPTA1, and SPTB genes. It is most commonly inherited in an autosomal dominant manner but may be inherited in an autosomal recessive manner in rare cases. Different types of hereditary spherocytosis are distinguished by severity and genetic cause.

Autosomal Dominant Inheritance:

About 75% of cases of hereditary spherocytosis are inherited in an autosomal dominant manner. This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause the condition.

When a person with a mutation passes on to the child for an autosomal dominant condition, each child has a 50% (1 in 2) chance to inherit that mutation.

 In rare cases, hereditary spherocytosis is inherited in an autosomal recessive manner.

A person must have inherited one mutated gene copy from each parent, who are referred to as genetic carriers.

When 2 carriers of an autosomal recessive condition have children, each child has a:

– 25% (1 in 4) chance to be affected

– 50% (1 in 2) chance to be an unaffected carrier like each parent

– 25% chance to be unaffected and not be a carrier

Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). By doing a full gene analysis of these genes, one can understand the risk of passing it on to their offspring.

 Any interesting case study or success story?

  • Ms Roopa, who is in her early 30s from Bangalore, reached out to me as she had a strong family history of breast cancer on the maternal side of the family. Ms Roopa’s mother and maternal aunt were diagnosed with breast cancer in their 40s and she was very worried about her potential risk of being diagnosed with Breast Cancer in future. As a genetic counsellor, I explained to Ms Roopa about the potential chances of inheriting a genetic mutation in one of the cancer-causing genes associated with breast cancer based on the family history she had described.
  • Ms Roopa was suggested to get her mother tested for a hereditary cancer panel consisting of breast cancer-causing genes. Based on the hereditary breast cancer panel analysis, it was found that Ms Roopa’s mother had a genetic mutation in PALB2 gene, which is strongly associated with Breast cancer, and this mutation is also known to increase the risk of pancreatic cancer and ovarian cancer.
  • The genetic mutation that was detected in Ms Roopa’s mother was tested for Ms Roopa and based on the analysis the same genetic mutation was inherited in the PALB2 gene. This led to an understanding that Ms Roopa has an increased risk for the above-mentioned hereditary cancer conditions.
  • As the genetic mutation present in the gene PALB2 follows an autosomal dominant mode of inheritance where there is 50% chance for the genetic mutation to be passed on to the offspring. Based on these interpretations and findings, specific screening and surveillance measures were suggested to Ms Roopa based on the National Comprehensive Cancer Network® (NCCN®). Due to the genetic mutation being present the surveillance and screening needs to start as early as the age of 30 onwards considering the family history and clinical data.
  • Ms Roopa was suggested to do Annual mammography with consideration of tomosynthesis along with consideration of annual breast MRI with contrast starting at age 30, with modification as appropriate based on family history by discussing with the physician.
  • Potential management options such as prophylactic risk-reducing mastectomy (surgery to remove one or both breasts to reduce the risk of developing breast cancer by up to 95%) was suggested as an option by having a discussion with the oncologist based on the family history.
  • Knowing if a PALB2 genetic mutation is present is advantageous. At-risk relatives, i.e., first/second-degree relatives, can be identified, enabling the pursuit of a diagnostic evaluation.
  • Getting the genetic test done has helped Ms Roopa be more proactive about her health and do these screenings from an early age onwards to help in potentially detecting any breast cancer tumours at the early stage of cancer for better treatment management purposes as most of the cancers do not show immediate symptoms and go undiagnosed till late stage of cancer-causing lesser chances of survival.
  • As a genetic counsellor, all the questions related to risk assessment, limitations of the genetic test, screening and surveillance options, and management options were discussed with Ms Roopa by giving her access to the right set of resources and a specialised doctor who can help her with overall process. More insights were provided based on the genetic findings to Ms Roopa and she was able to take her own choice based on the options provided by the genetic counsellor and the physician.
  • What are the things to keep in mind while opting for genetic testing/screening? What is its hope for medical science in the days to come?
  • Every genetic test is performed based on the situation. Individuals need to talk with their physician, geneticist or genetic counsellor to have a better understanding, especially when it comes to a diagnosis or a clinical condition.
  • There are things to keep in mind before deciding on a genetic test. Such as the test platform, test limitations, laboratory accreditations, measures taken to safeguard data and privacy, ability to access raw data. And most importantly, having access to genetic counsellors to understand the results to avoid undue stress and misinterpretation.
  • Accessibility of genetic tests has been dramatically increasing, and prices are still dropping to this day.
  • In 2006, the cost of sequencing one’s genes dropped to around $14 million. Less than ten years later, in 2015, that figure dropped to approximately $4,000. By the end of the same year, costs were as low as $1,500.
  • There are constant updates in the field of genetics. This means new data, scientific associations and massive large-scale studies are published frequently, which increases knowledge on various conditions. This indeed helps the community diagnose and prevent conditions from being passed on to the next generation.
  • Due to an increase in budget for research and development in the field of medical sciences, drug discovery and gene-therapies will be available for many rare conditions. This includes common health conditions that leads to personalised health solutions and precision medicine.
  • What are the services offered by Prenetics Ltd and what are the cost implications?

Depending on which CircleDNA kit one chooses, we provide different sets of information.

  • Vital kit (HK$1,192 ~ 11k INR) includes reports across 14 categories centring on diet, nutrition, fitness and overall wellness
  • Health kit (HK$3,192 ~ 30k INR) includes reports in four categories looking at health risks such as cancer and disease
  • Family Planning kit (HK$3,192 ~ 30k INR), made for those planning to conceive, is focused on the assessment of your carrier status for hereditary conditions.
  • Premium kit (HK3,992 ~ 37k INR) is the most comprehensive genetic test in the market, which offers more than 500+ reports across all categories.

Note that the CircleDNA results are not medical advice or report. They should not be used for diagnostic purposes. These tests are strictly meant to help individuals understand their genetic predispositions, where the results can be used to personalise their recommendations for optimum health.

For more details, refer to www.circledna.com

What are the numbers like? Is it popular or gaining popularity?

The CircleDNA direct-to-consumer test under Prenetics Ltd has been quite popular in Asia, South East Asia, UK and in European countries.

On an average the lab processes more than 15,000 samples per month.

What is the turnaround time for the test?

From the sample collection to the test results being ready in the CircleDNA app, the process takes around 3-4 weeks of time. The testing process is very simple. Using a cheek swab in the DNA collection kit, collect a saliva sample and send your sample back to the lab.

What are the diseases for which this screening works? 

CircleDNA is a comprehensive genetic test which consists of 500+ reports and tests for categories like Diet and Nutrition, Well-Being, Stress and Sleep, Pollution, Skin, Talents and Sports, Sports and Fitness, Success Traits, Music and Dance, Ancestry Test Results (with up to 15 geographical categories), Personality Traits, Behavioural Traits, Physical Traits, Gender Traits, Carrier Screening for understanding the risk of passing on the risk to the child (Family Planning), Hereditary Cancer risk.

The test helps an individual understand if h/she has inherited any mutation, increasing the risk for Cancers with a genetic basis, Dementia & Brain Health, common health risks such as obesity, stroke, and type 2 diabetes. Such health risks are very prevalent among the South Asian population.

Anu Acharya,
co founder and CEO of Mapmygenome

Anu Acharya, co-founder and CEO of Mapmygenome.

1) Explain genetic testing for a layman.

Genetic tests analyse your DNA. They can confirm or rule out disease, predict risk for disease, and assess the possibility of passing on abnormal genes to offspring. Depending on the purpose of testing, you may be recommend molecular testing, chromosomal testing, biochemical testing, or whole genome sequencing.

2) If I have hereditary spherocytosis, can I get to know the chances of it being carried by my offspring and how?

Hereditary Spherocytosis is a condition that affects the RBCs. One of the most common symptoms of Hereditary Spherocytosis is anaemia or reduced number of RBCs because of the breakdown of RBCs commonly associated with this condition. We can also oftentimes see jaundice – yellowing of the skin and eyes. Another common symptom is splenomegaly or enlargement of the spleen. These are common symptoms associated with Hereditary Spherocytosis and there are at least 5 well-established genes associated with the cause of the disease.

For someone who is diagnosed with Hereditary Spherocytosis, it is often natural to wonder about the chances of passing this on to the next generation. The answer to this condition really depends on which of the 5 genes are involved for a particular individual and family. That really decides whether the mode of transmission is dominant, where there would be 50% risk to the next generation or whether it is recessive, where there would be a 25% risk to the next generation. Having said that, the vast majority of nearly 75% of Hereditary Spherocytosis is inherited in an autosomal dominant manner and the most common gene that is involved is ANK1 gene. It becomes most important to understand what gene is involved in the family and the individual and genetic testing can help understand what gene is causing your Hereditary Spherocytosis. Once we have an understanding of that, then it is an easier process to understand if this gene is responsible for autosomal dominant condition or recessive condition. That can inform the recurrence risk or the chance of passing it on to the future generation.

It is really helpful to speak to your genetic counsellor so that they can document the medical history and family history, which can sometimes give a sense of what the inheritance pattern looks like. However, the best way to approach understanding what the risk is to the next generation is through genetic testing. Genetic counsellors are experts in medical genetics and psychological counselling and they can help facilitate genetic testing and also help you understand what your genetic test report means in terms of what is the gene involved, what is the inheritance pattern related to that particular gene, and what it means for any future children that you may have, the genetic testing that can help in future pregnancies, and to help make decisions about testing and management of the condition. There are management recommendations or guidelines for children born with the condition. The vast majority of people with the condition (60-70%) have a moderate form of the condition with symptoms of anaemia, jaundice, and splenomegaly. Nearly 3-5% have a severe form of the disease – they may require frequent transfusions and they may have skeletal development issues. The first step is to understand what gene is involved, and then the next steps can be discussed with the genetic counsellor. I would strongly recommend genetic counselling for you, for your family.

3) Any interesting case study or success story?

We have had several success stories related to weight loss, diabetes management, prevention of cardiovascular diseases and cancer, and in optimizing treatments. Many prominent physicians recommend our tests to their patients for confirming diagnosis and our genetic counselling sessions for informed choices. With the pandemic, we are seeing a growing demand for our immunity screening, nutrigenomics, and fitness genomics tests.

4) What are the things to keep in mind while opting for genetic testing/screening? What are its hope for medical science in the days to come?

Understand your health history. Consult with a doctor or genetic counsellor for better insights into health history, medical history, and lifestyle. This can help in preparing better for the test results, in devising mitigation plans, and in making informed choices. Sometimes, when there is a genetic condition in the family, it is better to discuss with the family to understand the implications to all members. Individuals with healthcare insurance often find out if the insurance provider covers the test costs.

Genetic testing is a nascent field, where technology is evolving. With these advances in technology, the scope of genetics in medical science keeps increasing.

5) What are the services offered by Mapmygenome?

  • Predictive genomics or personalized health solutions – Genomepatri, Myfitgene, MyNutriGene, SmartSport
  • Molecular diagnostics including Whole Exome Sequencing, Whole Genome Sequencing, and BRCA 1/2 Full Gene Sequencing.
  • Carrier screening, prenatal screening, new-born screening
  • Pharmacogenomics – MedicaMap
  • Ancestry testing
  • Genetic counselling
  • RT-PCR based infectious disease tests
  • COVID-19 – NABL and ICMR approved RT-PCR diagnostic test, Immunity testing (presymptomatic) including COVID risk and severity prediction, antibody testing

6) What are the numbers like? Is it popular or gaining popularity?

When we started offering personal genomics this was a new concept in India. We had to create awareness and build the market. Today, tens of thousands of people from various parts of the country and from abroad are our customers. In the last year, with the growing demand for healthier lifestyle, we have seen an increase in popularity.

7) What are the cost implications?

Predictive genomic testing is more like an investment plan – the earlier you start, the more benefits you derive. They cost a fraction of some of the modern treatment fees and amount cumulatively spent on regular health check-ups. Let us consider the benefits – with these tests, it becomes easier to switch to healthy lifestyle, to prevent or delay onset of disease, to manage lifestyle conditions such as diabetes, to help your doctors in choosing the best treatment plan that works for you, etc.

Molecular diagnostic tests on the other hand help in confirming diagnosis, thereby reducing the cost of diagnostic odyssey. Family members of patients with specific gene variants or mutations also encouraged to take up genetic testing as a screening method.

Overall, the benefits far outweigh the costs.

8) What are the diseases for which this screening works?

Our predictive genomics tests span several domains in healthcare – cardiovascular, lifestyle (diabetes, obesity, etc.), cancers, neuropsychiatric, skin, immunity, nutritional gaps, fitness and performance, autoimmune conditions, skin troubles and diseases, kidney health, gut health, bone health, gyanec health, habits (smoking, caffeine, alcohol, etc.), and more

9) What else does genetic screening/testing help in? 

  • To find your genetic risk for a disease, which can help you in preventing or delaying the onset of disease
  • To find your risk of passing on some genetic conditions to your offspring
  • To screen your baby or foetus
  • To confirm a clinical diagnosis
  • To understand disease biology and inheritance patterns
  • To determine the best treatment and management plans for a disease
  • To personalize your nutrition and fitness plans
  • To understand your genetic roots and ancestry
  • To understand what makes you unique and possibly eccentric

Dr Gurudutt Bhat, Consultant – Paediatrics, Fortis Hospital, Kalyan

Dr Gurudutt Bhat, Consultant – Paediatrics, Fortis Hospital, Kalyan.

What are the opportunities and challenges of genetic testing? 

The COVID19 pandemic has truly showcased India’s medical engineering talent, scientific expertise and the country’s potential to become a healthcare hub of the future. In this growth story, what stands out is India’s vast opportunity to achieve dramatic improvements in health outcomes. One way to that is genetic testing. Genetic testing has come a long way in preventive medicine, especially among pregnant women and their babies.

Blood and other tests are done mainly in pregnant women to rule out any diseases caused by a defect in the baby’s genes. It helps the expectant mother and her treating Obstetrician to manage the pregnancy and delivery appropriately. Some of the defects which can be detected are of the baby’s brain or spine etc. It can be an invasive test like a blood test or Amniotic Fluid Test, or non-invasive test like Ultrasonography. After the baby is born, its genetic sequencing can help confirm any gene mutations’ presence or absence. If the family already has an older child with genetic disorders, this test will help the subsequent baby be diagnosed early, and appropriate intervention can be initiated.

A great example of genetic screening is in older women who get pregnant after the age of 34yrs. These women are at high risk of having babies with Down’s Syndrome. Since it is a genetic disorder, the early screening will help detect such defects. This allows the family understand the consequences of the defect. They can undergo appropriate counseling, and it also helps the mother deliver the baby with proper precautions.

The biggest challenge for the success of genetic testing in India is its high cost. However, with the increasing use of genetic screening in India, the cost factor is slowly balancing out. Another problem area is that like everything else in medicine, this is not an exact science. There is a lot of evidence that still needs to be organized. There may be some problems with the tests available with some genetic testing companies, and not all tests are available easily in India.

When does genetic disorder get transmitted from a mother to her baby?

The defects in a mother’s X chromosome can be inherited by both male and female babies. A defect in Y chromosome can only be detected in a male baby. A defect in the other chromosome can be transmitted to a baby in two forms known as autosomal dominant i.e. the gene will express dominantly in the baby even if there is only one copy of that gene on a chromosome. In an autosomal recessive genetic conditions both copies of the gene are needed for expression.

If I have hereditary spherocytosis, can I get to know its chances being carried by my daughter?

Hereditary spherocytosis is a genetic defect leading to a defect in the spectrin protein, which make the red blood cell membranes fragile. This red blood cell breakdown causes anemia and its complications. Up to 75 % of hereditary spherocytosis cases are autosomal dominant gene induced hence can be seen in babies of mothers with this condition. Hence, early diagnosis and proper treatment can prevent complications.

Any interesting case study or success story?

A recent case of a girl with the genetic problem of Spino-Muscular Atrophy can be a classic example of a success story. Due to genetic screening, doctors were able to diagnose her medical condition. Her parents raised Rs 16 crores for her treatment with a new gene modifier drug. This is a testimonial to the future where early genetic testing can help find a cure and offer early interventions for some genetic conditions.

What are the things to keep in mind while opting for genetic testing? 

The idea for seeking genetic testing is to find way to prevent or treat certain conditions that we might be predisposed to. Decide which screening tests you need (to find a disease at an early stage when it might be more treatable), is important, so seek advice before testing:

  • Think about your reasons for wanting the test
  • Get the right tests
  • Ensure that you and your family are prepared for the results
  • Ensure that you have a personalized plan for dealing with the diagnosis

What is its hope for medical science in the days to come?

Genetic testing can help people make healthy choices. For instance, in a family that is predisposed to developing a certain kind of Colon Cancer or any other factors that can cause Cancer, genetic screening can help identify this risk. The opportunities this discipline offers for arriving at better health outcomes and personalized medicine are immense. We must realize that genetic testing has grown from a niche speciality for rare disorders to a broad scope of applications for routine, complex diseases and personal use. However, there is a need for healthcare providers, the diagnostic community and the government to step-up and uplift genetic diagnostics, making it available, accessible and safe for all.

Dr Udhaya Kotecha, Lead Clinical Geneticist, Neuberg Centre of Genomic Medicine

Dr Udhaya Kotecha, Lead Clinical Geneticist, Neuberg Centre of Genomic Medicine.

If I have hereditary spherocytosis, can I get to know its chances of being carried by my daughter? 

Hereditary spherocytosis is a condition where hemolytic anemia occurs due to destruction of red blood cells. Currently, five genes are known to be causative for this disorder (genetic heterogeneity: where a single disease can be caused by genetic disease, causing variation in more than one gene). A patient suspected of having hereditary spherocytosis can have the same due to genetic variation in any one of the five genes. It is commonly inherited in an autosomal dominant manner, meaning that if one of your gene copies is carrying the variant, you may manifest symptoms. There is a 50% chance that each of your offspring may inherit the disease-causing variant in this inheritance pattern. Rarely hereditary spherocytosis is caused by recessive mutations: meaning that both copies of the gene need to be alerted to have the disease. If you have hereditary spherocytosis due to a recessive mutation, the chances that your children will be affected depends on your partner’s carrier status. If your partner is also carrier, a disease-causing variant in the same gene, then there is a 75% chance of your children being affected. If your partner does not carry any genetic alteration in the same gene, then all your children will only be carriers, but none will be affected.

Dr Siddharth Srivastava, Chief Scientist (Molecular Oncology), Neuberg Center for Genomic Medicine

Dr Siddharth Srivastava, Chief Scientist (Molecular Oncology), Neuberg Center for Genomic Medicine.

What are the challenges of genetic testing?

The patient, their family members, consulting clinician/ medical geneticist, molecular pathologist, and genetic counsellor have stakes in the successful resolution of the patient’s problem. Interestingly all of them face different sets of challenges. Finding the genetic basis of diseases is a matter of speciality doctors. The first challenge the patient faces is navigating their way from general practice to these centres that are usually located in cities or large towns. The rarefied set of specialists doctors are further split into sub-speciality. Doctors who understand genetic basis of cancers or that of cardiovascular disorders, inherited diseases etc. To get to the right doctor, often naïve patients have to go through a maze of trial and error.

A conclusive diagnosis of such disorders or disease can be made by using molecular techniques. A dialogue between the consulting doctor and molecular pathologist sets up where the molecular pathologist understands the patient’s clinical history and clinician’s question. Accordingly s/he selects right test using most appropriate technique. This is crucial as molecular tests are complex, running into weeks and they are also expensive. For most accurate reports, the molecular pathologist should get detailed and accurate patient history which helps them to correlate molecular data and write accurate interpretations which will have deep implications on patient management. Acquiring patient’s clinical history is a challenge.

A lot of the times, diagnosis of the patient has implications on the immediate family members such as children, siblings, children of siblings. During the time of diagnosis of the patient, the “at risk” family members may seem to be leading a normal life. They do not feel concerned about their own chances of getting the disease in later parts of their lives. Genetic counsellors face tremendous challenges by collecting data from various family members and discussing the risks and convincing them to take the test.

Any interesting case study or success story?

Genomic testing has made both detection of inherited disorders, as well as treatment of complex diseases such as cancer and there, are countless success stories. There was a person from Mumbai whose mother (70 years old) was detected with breast cancer (ER+Her2- type). An extremely sharp cancer doctor was treating her with hormone therapy. After three years of treatment, she relapsed. This means that she stopped responding to the hormone treatment and the tumour grew despite getting the therapy. The doctor discussed with us at Neuberg Center of Genomic Medicine, and based on the clinical history, we predicted that most likely a defect in either ESR1 gene or PIK3CA gene may have resulted in the patient no longer responding to the treatment. If the defect was indeed in ESR1 gene, the doctor could changer her therapy to a drug called fulvestrant, and if the defect were in PIK3CA gene, then the drug would have changed to Alpelisib (approved by US FDA). However, the problem got compounded as the patient moved out of Mumbai, and the amount of tumour tissue was less to perform the test. We resorted to another test call liquid biopsy, where a tube full of patient blood was collected from her home and shipped to our laboratory. Indeed we detected a defect in PIK3CA, and the patient is now doing very well on Alpelisib therapy.

Another instance was that of a 45 years old man from Nashik who had prostate cancer. Since he was diagnosed at a young age with cancer, the clinical doctor suspected it to run in the family. The doctor connected with us, and one of our genetic counsellor spoke with the patient at length to get a history of cancers in the extended family. Patient’s mother had breast cancer at the age of 55, and she had since passed away. Genetic counsellor converts entire patient’s family history into the pedigree chart. Defects in BRCA genes and BRCAness genes could be the reason for the patient’s prostate cancer. If true, the patient could become eligible for a drug called Olaparib, and it would then become imperative to test his 15-year-old daughter too. We collected patient’s blood and tested for BRCA and BRCAness genes. Indeed the patient came positive for BRCA mutation. While it brought cheer to him, he also got concerned for his daughter. We tested the daughter and several of his “at risk” first and second-degree relatives. While his daughter had no pathogenic BRCA mutation, and she was considered as normal as any individual, patient’s 30 years old sister was detected positive with the same BRCA mutation. Thus the clinical doctor has kept her on active surveillance while doing periodic mammogram and breast exams.

What are the things to keep in mind while opting for genetic testing? What are its hope for medical science in the days to come?

While opting for genetic testing, one should know that either the blood or tissue sample would be asked from the patient. I would advice patients to collect their tissue samples from pathology labs if ever their biopsy is done. Usually the tests takes more than ten days to give out the results. Patients should take time to understand their report from the treating doctor and, if necessary, call the molecular pathologist. The patient should provide the detailed family history to the genetic counsellors.

The genetic basis of most complex diseases is being identified every passing day. Identifying the genetic cause helps to detect “at risk family members” and helps find newer therapies for the patient to manage disease such as cancer.

What are the diseases for which it works?

Most inherited disorders such as Down’s syndrome, thalassemia/haemophilia, muscle dystrophy/spinal muscular atrophy can be detected using genetic testing. Genetic testing is also used in prenatal diagnosis, recurrent abortions, infertility, mental retardation. In complex diseases such as cancers, genomic testing can diagnose and give newer and better treatment options. Approximately, 6,000 genes are known to cause human disorders, and the same can be tested via different genetic tests. The rapid rate of gene discovery is increasing the number of diseases known on an almost daily basis.