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

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 wit...

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Bibliographic Details
Published in:European journal of human genetics : EJHG 2017-06, Vol.25 (7), p.889-893
Main Authors: Redler, Silke, Strom, Tim M, Wieland, Thomas, Cremer, Kirsten, Engels, Hartmut, Distelmaier, Felix, Schaper, Jörg, Küchler, Alma, Lemke, Johannes R, Jeschke, Stephanie, Schreyer, Nicole, Sticht, Heinrich, Koch, Margarete, Lüdecke, Hermann-Josef, Wieczorek, Dagmar
Format: Article
Language:English
Subjects:
Adaptor Proteins, Vesicular Transport - genetics
Ataxia
Brain research
Cerebellum
Child
Child, Preschool
Epilepsies, Myoclonic - diagnosis
Epilepsies, Myoclonic - genetics
Epilepsy
Ethics
Female
Genes, Recessive
Genetics
Humans
Intellectual disabilities
Intellectual Disability - diagnosis
Intellectual Disability - genetics
Male
Mutation
Nerve Tissue Proteins - genetics
Patients
Phenotype
Phenotypes
Proteins
Short Report
Syndrome
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Summary: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.
ISSN:1018-4813
1476-5438
DOI:10.1038/ejhg.2017.52