E-mail ID : info@iamg.in |
Online Submission |
Click Here For Online Submission |
Instructions for authors |
Genetic Clinics |
Editorial board |
Get Our Newsletter |
Subscribe |
Send Your Feedback |
Feedback Form |
About Us |
IAMG |
GeneFocus
Superspecialists | 30 |
Nephrology | 3 |
Gastro-medicine | 4 |
Cardiology | 6 |
Clinical Immunology | 3 |
Critical care Medicine | 2 |
Endocrinology | 1 |
Paediatric Gastroenterology | 1 |
Urology | 4 |
Neurosurgery | 1 |
Neurology | 5 |
Specialists | 70 |
Pediatrics | 19 |
Obstetrics and Gynaecology | 21 |
Ophthalmology | 2 |
Radiotherapy and oncology | 8 |
General Medicine | 10 |
Orthopedics | 5 |
Psychiatry | 2 |
General Surgery | 3 |
The study results show that only half (53%) of the participants had ever heard of ES. But, if we analyse data in groups, 93% (28/30) of superspecialist doctors had heard about ES as compared to 36% (25/70) of the specialist doctors. Only 30% of participants were previously aware of the information and issues related to exome sequencing. None of the specialist doctors had ordered ES but 16% (5/30) superspecialist doctors had previously ordered ES and 80% (4/5) of them had found it to be useful in their patient management. Most of the clinicians (87%) agreed that ES is a useful diagnostic technique and 84% of participants opted for more information on exome sequencing. Thirty-one percent of the participants felt that they would be prepared to deal with the issues related to exome sequencing when a patient brings a report of exome sequencing.
Besides the established use of ES in the diagnosis of single gene defects, 30% participants said the use of ES for preconceptional carrier screen appealed most to them, around 29% said ES for prenatal testing of fetus appealed to them and 15% participants said none of the other uses appealed to them (Figure 1). The use of ES for newborn screening is a matter of active research and in pilot phases of research (Berg et al., 2017). On being asked if the clinicians would consider exome sequencing for newborn screening, 20% of participants said yes, 11% were not sure and the rest 69% were not in favor of ES for newborn screening. Most participants felt that if they did exome sequencing of a newborn, as a part of newborn screening, they would like to know the treatable genetic conditions and the carrier status for recessive diseases which can have only reproductive implications (Table 2).
Disease condition | Yes | No | Not |
sure | |||
Treatable genetic disease | 96 | – | 4 |
Untreatable genetic conditions | 37 | 53 | 10 |
Late onset genetic conditions | 49 | 40 | 11 |
Carrier status of recessive | 56 | 36 | 8 |
diseases for reproductive | |||
implications | |||
In response to the option of getting their exomes sequenced, 33% of participants said they would like to go ahead. The reasons cited for opting for ES were to know their risk for multifactorial diseases and take preventive actions (61%), general curiosity (15%), carrier status for reproductive planning (12%) and pharmacogenomic testing (6%) (Figure 2).
We asked participants which authority should decide regarding the inclusion of incidental findings (IF) in ES reports. Around 36% of participants said the in-charge doctor should decide; another 36% said that the patient themselves should decide;13% were of an opinion that a central body should decide, and 2% of participants thought that the testing laboratory should decide (Figure 3). When asked which incidental findings should be shared in the ES report of the patient, 40% of participants considered incidental findings of diseases where early diagnosis can lead to treatment should be shared and 23% of participants said incidental findings should be shared according to patient’s own choice. Around 17% percent said all disease mutations should be shared in ES, 14% said pharmacogenetic and treatable conditions should be shared and 2% said no IF should be shared (Figure 4).
Patients with monogenic disorders are first seen by physicians who are specialists but not medical geneticists. Some of the specialists and superspecialists have started ordering ES though the numbers may be small. As the number of medical geneticists in India is small, a greater number of non-geneticists will be taking care of patients and families with genetic disorders. For appropriate ordering and interpretation of ES, physicians need to be aware of the principle of the NGS, interpretation of sequence variations and related issues. The results of this small study try to get an idea at present of the Indian scenario. About half of the participants knew of ES and most of them felt that this is a useful diagnostic technique and opted for more information on exome sequencing. In our study, 33% of participants said that they would like to get their exome sequenced which is lesser than similar studies in developed nations (including genetic and non-genetic professionals) where 49-77% of participants expressed their desire to get their ES. This probably reflects the fact that our participants are not as informed and familiar with ES. The secondary/incidental findings detected in ES have always been an area of major debate and the ACMG periodically releases its statement to address this issue (Kalia et al., 2017). In a study of genetics professionals to learn about their attitudes towards the return of incidental results from ES, 50% thought that offered results should not be limited to those deemed clinically actionable and the vast majority (81%) thought that individual preferences should guide return of the results (Yu et al., 2014). In another study by Lemke et al. most genetic professionals said that most importantly, two types of findings i.e. adult-onset clinically actionable disease, and a childhood-onset non-clinically actionable disease should be disclosed to patients. In another study, non-genetic professionals laid impetus on actionable findings but expressed that even ‘not clinically actionable’ findings should also be made available (Strong et al, 2014). A study of non-genetic professionals from Greece reported that clinically valid and actionable IFs should be returned, but always with caution and taking into consideration the patients’ wishes, although several experts reported returning IFs according to their clinical discretion (Gourna et al, 2014). When compared to previous studies, the non-geneticist clinicians in our study also held the same views favoring sharing of actionable incidental findings but also many expressed views ranging from providing all disease-causing mutations in ES report to those advocating that it should be based solely on the patients’ choice.
Thirty-one percent of participants felt that they would be prepared for ordering ES. This was their personal opinion and this study did not judge the capabilities. In the questions and comments section, the participants asked about the availability of ES, cost, turnaround time, limitations and commented that basic genetic training should be included in the medical curriculum, as presently no medical genetics training is provided at any level of education in the medical curriculum. This reinforces the participants’ interest in ES and their desire to use it for patient management.
One of the main causes of bias in our study could be related to questionnaire design. No pilot testing of the study questionnaire was done. The questions drafted were hypothetical and sometimes complex. While answering many questions, the participants could have been confused about whether to answer the question for self or the patient. It is possible that inclusion of the information sheet aimed at providing a minimum level of genetics education, itself introduced an unintended bias. Other causes of bias would be a small study sample size, many participants being friends of the authors and belonging to nearby institutes, this study does not represent the views of non-geneticist clinicians across India.
As more private laboratories keep pushing ES for diagnostic and screening purposes into clinics and more clinicians order ES, they might require more support from genetic health professionals to understand and interpret genomic laboratory reports and help with genetic counseling. Also, in the field of medical genetics, knowledge and scientific understanding are constantly developing. In developing countries like India, the genetic health professional support mechanisms are limited. This lacuna might lead to the decreased utility of ES, where we might miss guiding patients for timely health care intervention to ameliorate disease effects, facilitate carrier testing, prenatal diagnosis and genetic counseling. Realizing this unaddressed need, in recent years, a nation-wide framework of collaborative research initiatives catering to the rare disease community and provision of training in medical genetics have emerged (GUaRDIAN Consortium, 2019) (Aggarwal & Phadke, 2015).
In a large and heterogeneous country like India it is vital that training and awareness in medical genetics be inculcated at the level of undergraduate medical school and residency and through continuing medical education programs. As the medical genetics community in the world is trying to deal with waves of ethical and psychological dilemmas arising from the powerful technique of ES, we are trying to get an idea about awareness of ES amongst clinicians without formal training in medical genetics, to take up the challenge of large scale meaningful use of ES and other next-generation sequencing-based diagnostics.
Acknowledgments: We wish to thank all the study participants.
Dr. Meenakshi Lallar and Dr. Shubha Phadke declare that they have no conflict of interest.
The questionnaire and information sheet used for the study are provided as Supplementary material with the online version of the journal.
1. Aggarwal S, Phadke SR. Medical genetics and genomic medicine in India: current status and opportunities ahead. Mol Genet Genom Med 2015;160–171.
2. Berg JS, et al. Newborn Sequencing in Genomic Medicine and Public Health. Pediatrics 2017;139(2). pii: e20162252. doi: 10.1542/peds.2016-2252.
3. Gourna EG, et al. Incidental findings from clinical sequencing in Greece: reporting experts’ attitudes. J Community Genet 2014; 5: 383–393.
4. GUaRDIAN Consortium, et al. Genomics of rare genetic diseases-experiences from India. Hum Genomics. 2019; 14: 52.
5. Helmy M, et al. Limited resources of genome sequencing in developing countries: Challenges and solutions. Appl Transl Genom 2016; 9:15–19.
6. Kalia SS, et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): A policy statement of the American College of Medical Genetics and Genomics. Genet Med 2016;19: 249–255.
7. Kalynchuk EJ, et al. Prenatal whole-exome sequencing: parental attitudes. Prenat Diagn 2015; 35:1030-1036.
8. Lemke AA, et al. Perspectives of clinical genetics professionals toward genome sequencing and incidental findings: a survey study. Clin Genet 2013; 84: 230–236.
9. Meng L, et al. Use of exome sequencing for infants in intensive care units: ascertainment of severe single-gene disorders and effecton medical management. JAMA Pediatr 2017;171: e173438.
10. Nussbaum RL, et al. Thompson & Thompson Genetics in Medicine (8th edition). Philadelphia, Saunders/Elsevier, 2016.
11. Sapp JC, et al. Parental attitudes, values, and beliefs to- ward the return of results from exome sequencing in children. Clin Genet 2014; 85:120–126.
12. Strong KA, et al. Views of primary care providers regarding the return of genome sequencing incidental findings. Clin Genet 2014; 86: 461–468.
13. Verma A. Empowering the neurogenetic testing services in developing countries: use the basic skills with speed and scale. Ann Neurosci 2015; 22:1–3.
14. World Health Organization. Medical genetic services in developing countries. 2006. Retrieved from https://www.who.int/genomics/publications/GTS-MedicalGeneticServices-oct06.pdf
Abstract | Download PDF |