NECAP1 loss of function leads to a severe infantile epileptic encephalopathy

Journal of Medical Genetics
Anas M AlazamiFowzan S Alkuraya

Abstract

Epileptic encephalopathy is a broad clinical category that is highly heterogeneous genetically. To describe a multiplex extended consanguineous family that defines a molecularly novel subtype of early infantile epileptic encephalopathy. Autozygosity mapping and exome sequencing for the identification of the causal mutation. This was followed by expression analysis of the candidate gene. In an extended multigenerational family with six affected individuals, a single novel disease locus was identified on chromosome 12p13.31-p13.2. Within that locus, the only deleterious novel exomic variant was a homozygous truncating mutation in NECAP1, encoding a clathrin-accessory protein. The mutation was confirmed to trigger nonsense-mediated decay. Consistent with previous reports, we show that NECAP1 is highly enriched in the central nervous system. NECAP1 is known to regulate clathrin-mediated endocytosis in synapses. The mutation we report here links for the first time this trafficking pathway in early infantile epileptic encephalopathy.

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Citations

Jun 19, 2014·Epilepsy Currents·Andrew Escayg, Jennifer C Wong
Nov 26, 2015·European Journal of Human Genetics : EJHG·Katia HardiesArvid Suls
Aug 26, 2015·Genome Medicine·Candace T Myers, Heather C Mefford
May 25, 2015·Revue neurologique·G Lesca, C Depienne
Oct 22, 2014·Molecular Genetics & Genomic Medicine·Fowzan S Alkuraya
Sep 25, 2018·Journal of Neurogenetics·Jeffrey D Calhoun, Gemma L Carvill
Nov 2, 2019·Annals of Clinical and Translational Neurology·Hisato SuzukiToshiki Takenouchi
Aug 11, 2019·Annual Review of Cell and Developmental Biology·Esteban C Dell'Angelica, Juan S Bonifacino
Nov 1, 2015·Arquivos de neuro-psiquiatria·Marina C GonsalesIscia Lopes-Cendes
Jun 9, 2016·Human Molecular Genetics·Elizabeth E PalmerWilliam R Lagor
Dec 14, 2018·Epilepsia Open·Saud AlsahliFuad Al Mutairi
May 21, 2020·Disease Models & Mechanisms·Rebecca YarwoodMartin Lowe
Aug 12, 2019·Epilepsy & Behavior : E&B·Pedro H M MagalhãesIscia Lopes-Cendes

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