title: TSC2 c.1864C>T variant associated with mild cases of tuberous sclerosis complex.
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. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Farach
authors.affiliation: Department of Medical Genetics, BC Children's Hospital and UBC, Vancouver, British Columbia, Canada.
authors.forename: William T
authors.initials: WT
authors.lastname: Gibson
authors.affiliation: Division of Neurology, Texas Scottish Rite Hospital for Children and University of Texas Southwestern Medical School, Dallas, Texas.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Sparagana
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Nellist
authors.affiliation: Department of Clinical Genetics and School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center (MUMC), Maastricht, The Netherlands.
authors.forename: Connie T R M
authors.initials: CT
authors.lastname: Stumpel
authors.affiliation: Department of Clinical Genetics and Department of Medical Biochemistry and Genetics, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Marja
authors.initials: M
authors.lastname: Hietala
authors.affiliation: Department of Diagnostic and Interventional Imaging, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Elliott
authors.initials: E
authors.lastname: Friedman
authors.affiliation: Division of Child and Adolescent Psychiatry, Department of Psychiatry, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Pearson
authors.affiliation: Department of Medical Genetics, BC Women's Hospital and UBC, Vancouver, British Columbia, Canada.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Creighton
authors.affiliation: Department of Clinical Genetics and School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center (MUMC), Maastricht, The Netherlands.|Koraalgroep, Maasveld, Maastricht, The Netherlands.
authors.forename: Annemiek
authors.initials: A
authors.lastname: Wagemans
authors.affiliation: Medical Genetics Institute, Shaare Zedek Medical Center and the Hebrew University School of Medicine, Jerusalem, Israel.
authors.forename: Reveel
authors.initials: R
authors.lastname: Segel
authors.affiliation: Department of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Ben-Shalom
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Kit Sing
authors.initials: KS
authors.lastname: Au
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Hope
authors.initials: H
authors.lastname: Northrup
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012207:Rhabdomyoma / Q000175:diagnosis / Q000235:genetics / Q000601:surgery; D012720:Severity of Illness Index; D014402:Tuberous Sclerosis / Q000175:diagnosis* / Q000235:genetics*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
keywords: TSC2; genetic counseling; genotype-phenotype association; rhabdomyoma; tuberous sclerosis complex