Pathogenic RET Variants Occur at Higher Prevalence Than Previously Recognized Interview with:

Emily J. Gallagher, MDAssistant Professor of MedicineEndocrinology, Diabetes and Bone DiseaseIcahn School of Medicine at Mount Sinai 

Dr. Gallagher

Emily J. Gallagher, MD
Assistant Professor of Medicine
Endocrinology, Diabetes and Bone Disease
Icahn School of Medicine at Mount Sinai What is the background for this study?

Response: Multiple Endocrine Neoplasia Syndrome Type 2 (MEN2) is an inherited endocrine disorder characterized by the development of pheochromocytoma, medullary thyroid carcinoma (MTC) and parathyroid tumors. It occurs due to activating missense variants in the RET gene.

The estimated prevalence of MEN2 is 1 per 30,000 in the general population. Through a collaboration between The Center for Genomic Health, the Charles Bronfman Institute for Personalized Medicine, and the Division of Endocrinology at Mount Sinai, our aim was to investigate the prevalence and clinical manifestations of pathogenic RET variants in the multi-ethnic BioMe Biobank.

The BioMe Biobank is an electronic health record-linked biobank with exome sequencing data available for more than 30,000 patients recruited across The Mount Sinai Health System. What are the main findings?

Response: We found that the prevalence of pathogenic RET variant carriers in BioMe was approximately 1 in 2000. Five pathogenic RET variants were identified among 15 people. Three people were carriers of the p.Cys634Arg variant, and all three had MTC and had previously been identified from clinical practice as having MEN2A. None of the twelve other pathogenic RET variant carriers were known to have MEN2 from medical records. The most frequent variant in our study was the p.Val804Met variant. What should readers take away from your report?

Response:  The results from this study in the multi-ethnic BioMe Biobank reveal a higher prevalence of pathogenic RET variants than previously recognized. Carriers of pathogenic RET variants demonstrate highly variable expressivity for endocrine traits, including MTC. What recommendations do you have for future research as a result of this study?

Response:  Future research should focus on better understanding the penetrance and clinical impact of RET variants. For example, by screening for pathogenic RET variants, we can learn more about the rate and age of onset of MTC, enabling improved surveillance and treatment strategies for MEN2. Is there anything else you would like to add?

Response: The role of genomics in medicine is expanding, and genomic information will soon be integrated more broadly into clinical care. A major goal of Noura Abul-Husn, MD, PhD, Clinical Director of the Center for Genomic Health at the Icahn School of Medicine at Mount Sinai, is to train residents and fellows, such as Heidi Guzman, MD, an endocrinology fellow at the Icahn School of Medicine at Mount Sinai, and lead author on this abstract, in genomic screening and the integration of genomic medicine into clinical practice.

Any disclosures:  H. Guzman: None. E.J. Gallagher: None. G.M. Belbin: None. S. Cullina: None. R.S. Haber: None. J. Cho: None. E.E. Kenny: None. N.S. Abul-Husn: Previously employed at Regeneron Pharmaceuticals. Thank you for your contribution to the community.


ENDO 2019 abstract:

Exome Sequencing Reveals that Pathogenic RET Variants Occur at Higher Prevalence Than Previously Recognized: Data from a US Health System Biobank

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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