Variants in CPLX1 in two families with autosomal-recessive severe infantile myoclonic epilepsy and ID

Redler S, Strom TM, Wieland T, Cremer K, Engels H, Distelmaier F, Schaper J, Kuchler A, Lemke JR, Jeschke S, Schreyer N, Sticht H, Koch M, Luedecke HJ, Wieczorek D (2017)

Publication Type: Journal article

Publication year: 2017

Journal

European Journal of Human Genetics Nature Publishing Group: Open Access Hybrid Model Option B

Book Volume: 25

Pages Range: 889-893

Journal Issue: 7

DOI: 10.1038/ejhg.2017.52

Abstract

For a large number of individuals with intellectual disability (ID), the molecular basis of the disorder is still unknown. However, whole-exome sequencing (WES) is providing more and more insights into the genetic landscape of ID. In the present study, we performed trio-based WES in 311 patients with unsolved ID and additional clinical features, and identified homozygous CPLX1 variants in three patients with ID from two unrelated families. All displayed marked developmental delay and migrating myoclonic epilepsy, and one showed a cerebellar cleft in addition. The encoded protein, complexin 1, is crucially involved in neuronal synaptic regulation, and homozygous Cplx1 knockout mice have the earliest known onset of ataxia seen in a mouse model. Recently, a homozygous truncating variant in CPLX1 was suggested to be causative for migrating epilepsy and structural brain abnormalities. ID was not reported although it cannot be completely ruled out. However, the currently limited knowledge on CPLX1 suggests that loss of complexin 1 function may lead to a complex but variable clinical phenotype, and our findings encourage further investigations of CPLX1 in patients with ID, developmental delay and myoclonic epilepsy to unravel the phenotypic spectrum of carriers of CPLX1 variants.

Authors with CRIS profile

Heinrich Sticht Professur für Bioinformatik

Involved external institutions

Heinrich-Heine-Universität Düsseldorf DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Universität Duisburg-Essen (UDE) DE Germany (DE) Universität Leipzig DE Germany (DE) Universität Witten/Herdecke DE Germany (DE)

How to cite

APA:

Redler, S., Strom, T.M., Wieland, T., Cremer, K., Engels, H., Distelmaier, F.,... Wieczorek, D. (2017). Variants in CPLX1 in two families with autosomal-recessive severe infantile myoclonic epilepsy and ID. European Journal of Human Genetics, 25(7), 889-893. https://doi.org/10.1038/ejhg.2017.52

MLA:

Redler, Silke, et al. "Variants in CPLX1 in two families with autosomal-recessive severe infantile myoclonic epilepsy and ID." European Journal of Human Genetics 25.7 (2017): 889-893.

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