1. TSC2 c.1864C > T Variant Aassociated with Mild Cases of Tuberous Sclerosis Complex
- Author
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Laura S. Farach, Marja Hietala, Reveel Segel, Kit Sing Au, Deborah A. Pearson, Hope Northrup, Steven Sparagana, Efrat Ben-Shalom, Connie T.R.M. Stumpel, Annemiek Wagemans, Elliott R. Friedman, Susan P. Creighton, Mark Nellist, William T. Gibson, Clinical Genetics, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), and Klinische Genetica
- Subjects
Male ,0301 basic medicine ,tuberous sclerosis complex ,Rhabdomyoma ,PHENOTYPE ,Severity of Illness Index ,Tuberous sclerosis ,0302 clinical medicine ,Tuberous Sclerosis ,Intellectual disability ,rhabdomyoma ,MUTATIONAL ANALYSIS ,Child ,Genetics (clinical) ,Brain ,Magnetic Resonance Imaging ,Pedigree ,GENOTYPE ,medicine.anatomical_structure ,Child, Preschool ,genotype-phenotype association ,Female ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,GENES ,Genetic counseling ,ta3111 ,03 medical and health sciences ,Tuberous Sclerosis Complex 2 Protein ,Severity of illness ,Genetics ,medicine ,Humans ,Alleles ,Genetic Association Studies ,genetic counseling ,business.industry ,Tumor Suppressor Proteins ,Infant, Newborn ,medicine.disease ,Dermatology ,TSC2 ,nervous system diseases ,030104 developmental biology ,SEVERITY ,Amino Acid Substitution ,Mutation ,Autism ,TSC1 ,business ,030217 neurology & neurosurgery - 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.
- Published
- 2017
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