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Eur J Hum Genet. 2017 Jun;25(7):889-893. doi: 10.1038/ejhg.2017.52. Epub 2017 Apr 19.

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

Author information

Heinrich-Heine-University, Medical Faculty, Institute of Human Genetics, Düsseldorf, Germany.
Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Heinrich-Heine-University, Medical Faculty, Department of Diagnostic and Interventional Radiology, Düsseldorf, Germany.
Institute of Human Genetics, University of Duisburg-Essen, Essen, Germany.
Institute of Human Genetics, University of Leipzig, Leipzig, Germany.
Institute of Biochemistry, University of Erlangen-Nuremberg, Erlangen, Germany.
Children's Hospital Datteln, University Witten/Herdecke, Datteln, Germany.


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.

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