TY - JOUR
T1 - TSC2 c.1864C>T variant associated with mild cases of tuberous sclerosis complex
AU - Farach, Laura S.
AU - Gibson, William T.
AU - Sparagana, Steven P.
AU - Nellist, Mark
AU - Stumpel, Connie T R M
AU - Hietala, Marja
AU - Friedman, Elliott
AU - Pearson, Deborah A.
AU - Creighton, Susan P.
AU - Wagemans, Annemiek
AU - Segel, Reveel
AU - Ben-Shalom, Efrat
AU - Au, Kit Sing
AU - Northrup, Hope
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - TSC2
KW - genetic counseling
KW - genotype–phenotype association
KW - rhabdomyoma
KW - tuberous sclerosis complex
UR - http://www.scopus.com/inward/record.url?scp=85013177522&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85013177522&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.38083
DO - 10.1002/ajmg.a.38083
M3 - Article
C2 - 28211972
AN - SCOPUS:85013177522
SN - 1552-4825
VL - 173
SP - 771
EP - 775
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 3
ER -