A1 Refereed original research article in a scientific journal
TSC2 c.1864C > T Variant Aassociated with Mild Cases of Tuberous Sclerosis Complex
Authors: Farach LS, Gibson WT, Sparagana SP, Nellist M, Stumpel CTRM, Hietala M, Friedman E, Pearson DA, Creighton SP, Wagemans A, Segel R, Ben-Shalom E, Au KS, Northrup H
Publisher: WILEY
Publication year: 2017
Journal: American Journal of Medical Genetics Part A
Journal name in source: AMERICAN JOURNAL OF MEDICAL GENETICS PART A
Journal acronym: AM J MED GENET A
Volume: 173
Issue: 3
First page : 771
Last page: 775
Number of pages: 5
ISSN: 1552-4825
eISSN: 1552-4833
DOI: https://doi.org/10.1002/ajmg.a.38083
Abstract
Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disorder with variable expressivity associated with hamartomatous tumors, abnormalities of the skin, and neurologic problems including seizures, intellectual disability, and autism. TSC is caused by pathogenic variants in either TSC1 or TSC2. In general, TSC2 pathogenic variants are associated with a more severe phenotype than TSC1 pathogenic variants. Here, we report a pathogenic TSC2 variant, c.1864C>T, p.(Arg622Trp), associated with a mild phenotype, with most carriers meeting fewer than two major clinical diagnostic criteria for TSC. This finding has significant implications for counseling patients regarding prognosis. More patient data are required before changing the surveillance recommendations for patients with the reported variant. However, consideration should be given to tailoring surveillance recommendations for all pathogenic TSC1 and TSC2 variants with documented milder clinical sequelae. (C) 2017 Wiley Periodicals, Inc.
Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disorder with variable expressivity associated with hamartomatous tumors, abnormalities of the skin, and neurologic problems including seizures, intellectual disability, and autism. TSC is caused by pathogenic variants in either TSC1 or TSC2. In general, TSC2 pathogenic variants are associated with a more severe phenotype than TSC1 pathogenic variants. Here, we report a pathogenic TSC2 variant, c.1864C>T, p.(Arg622Trp), associated with a mild phenotype, with most carriers meeting fewer than two major clinical diagnostic criteria for TSC. This finding has significant implications for counseling patients regarding prognosis. More patient data are required before changing the surveillance recommendations for patients with the reported variant. However, consideration should be given to tailoring surveillance recommendations for all pathogenic TSC1 and TSC2 variants with documented milder clinical sequelae. (C) 2017 Wiley Periodicals, Inc.
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