Gonadal mosaicism of a novel IQSEC2 variant causing female limited intellectual disability and epilepsy.

Autor: Ewans LJ; St Vincent's Clinical School, University of New South Wales, Darlinghurst, New South Wales, Australia.; Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia., Field M; The Genetics of Learning Disability Service, Waratah, New South Wales, Australia., Zhu Y; The Genetics of Learning Disability Service, Waratah, New South Wales, Australia., Turner G; The Genetics of Learning Disability Service, Waratah, New South Wales, Australia., Leffler M; The Genetics of Learning Disability Service, Waratah, New South Wales, Australia., Dinger ME; St Vincent's Clinical School, University of New South Wales, Darlinghurst, New South Wales, Australia.; Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia., Cowley MJ; St Vincent's Clinical School, University of New South Wales, Darlinghurst, New South Wales, Australia.; Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia., Buckley MF; SEALS Molecular and Cytogenetics Laboratories, Randwick Hospitals Campus, Sydney, New South Wales, Australia., Scheffer IE; Epilepsy Research Centre, Department of Medicine, University of Melbourne Austin Health, Melbourne, Victoria, Australia.; Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia.; Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Victoria, Australia., Jackson MR; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia., Roscioli T; St Vincent's Clinical School, University of New South Wales, Darlinghurst, New South Wales, Australia.; Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.; Sydney Children's Hospital, University of New South Wales, Sydney, New South Wales, Australia., Shoubridge C; Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.; Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2017 Jun; Vol. 25 (6), pp. 763-767. Date of Electronic Publication: 2017 Mar 15.
DOI: 10.1038/ejhg.2017.29
Abstrakt: We report a family with four girls with moderate to severe intellectual disability and epilepsy. Two girls showed regression in adolescence and died of presumed sudden unexpected death in epilepsy at 16 and 22 years. Whole exome sequencing identified a truncating pathogenic variant in IQSEC2 at NM_001111125.2: c.2679_2680insA, p.(D894fs*10), a recently identified cause of epileptic encephalopathy in females (MIM 300522). The IQSEC2 variant was identified in both surviving affected sisters but in neither parent. We describe the phenotypic spectrum associated with IQSEC2 variants, highlighting how IQSEC2 is adding to a growing list of X-linked genes that have a female-specific phenotype typically associated with de novo mutations. This report illustrates the need for careful review of all whole exome data, incorporating all possible modes of inheritance including that suggested by the family history.
Databáze: MEDLINE
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