Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Determining the pathogenicity of patient-derived TSC2 mutations by functional characterization and clinical evidence

Dunlop, Elaine A., Dodd, Kayleigh M., Land, Stephen C, Davies, Peter A., Martins, Nicole, Stuart, Helen, McKee, Shane, Kingswood, Chris, Saggar, Anand, Corderio, Isabel, Medeira, Ana Maria Duarte, Kingston, Helen, Sampson, Julian Roy, Davies, David Mark and Tee, Andrew 2011. Determining the pathogenicity of patient-derived TSC2 mutations by functional characterization and clinical evidence. European Journal of Human Genetics 19 (7) , pp. 789-795. 10.1038/ejhg.2011.38

Full text not available from this repository.

Abstract

Tuberous sclerosis complex (TSC) is a genetic condition characterized by the growth of benign tumours in multiple organs, including the brain and kidneys, alongside intellectual disability and seizures. Identification of a causative mutation in TSC1 or TSC2 is important for accurate genetic counselling in affected families, but it is not always clear from genetic data whether a sequence variant is pathogenic or not. In vitro functional analysis could provide support for determining whether an unclassified TSC1 or TSC2 variant is disease-causing. We have performed a detailed functional analysis of four patient-derived TSC2 mutations, E92V, R505Q, H597R and L1624P. One mutant, E92V, functioned similarly to wild-type TSC2, whereas H597R and L1624P had abnormal function in all assays, consistent with available clinical and segregation information. One TSC2 mutation, R505Q, was identified in a patient with intellectual disability, seizures and autistic spectrum disorder but who did not fulfil the diagnostic criteria for TSC. The R505Q mutation was also found in two relatives, one with mild learning difficulties and one without apparent phenotypic abnormality. R505Q TSC2 exhibited partially disrupted function in our assays. These data highlight the difficulties of assessing pathogenicity of a mutation and suggest that multiple lines of evidence, both genetic and functional, are required to assess the pathogenicity of some mutations.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Uncontrolled Keywords: TSC, mutation, function, pathogenicity
Publisher: Nature Publishing Group
ISSN: 1018-4813
Last Modified: 08 Aug 2019 21:25
URI: http://orca-mwe.cf.ac.uk/id/eprint/30151

Citation Data

Cited 3 times in Google Scholar. View in Google Scholar

Cited 7 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item