title: Oligophrenin 1 (OPHN1) gene mutation causes syndromic X-linked mental retardation with epilepsy, rostral ventricular enlargement and cerebellar hypoplasia.
abstract: We identified an oligophrenin 1 (OPHN1) gene mutation in a family with five brothers affected by a recognizable pattern of clinical and neuroradiological hallmarks. The distinctive phenotype comprised moderate to severe mental retardation, myoclonic-astatic epilepsy, ataxia, strabismus and hypogenitalism. Neuroimaging displayed fronto-temporal atrophy with rostral enlargement of the lateral ventricles, lower vermian agenesis and asymmetric cerebellar hypoplasia. Mutation analysis of the OPHN1 gene on Xq12 disclosed a genomic deletion of exon 19 causing a frameshift. Notably, OPHN1 mutations have been previously reported as a rare cause of non-syndromic X-linked mental retardation. Our findings, however, indicate that OPHN1 mutations result in a recognizable syndrome. In addition, identification of OPHN1 as a further gene associated with epileptic seizures will help to unravel aetiologic factors of epilepsy.
authors.affiliation: Department of Human Genetics, Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany. cbergmann@ukaachen.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Bergmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Zerres
authors.forename: Jan
authors.initials: J
authors.lastname: Senderek
authors.forename: Sabine
authors.initials: S
authors.lastname: Rudnik-Schoneborn
authors.forename: Thomas
authors.initials: T
authors.lastname: Eggermann
authors.forename: Martin
authors.initials: M
authors.lastname: Häusler
authors.forename: Michael
authors.initials: M
authors.lastname: Mull
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ramaekers
mesh_terms: D001483:Base Sequence; D002531:Cerebellum / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins; D004831:Epilepsies, Myoclonic / Q000235:genetics; D005260:Female; D020690:GTPase-Activating Proteins; D017353:Gene Deletion; D006801:Humans; D020547:Lateral Ventricles / Q000473:pathology; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics*; D016415:Sequence Alignment; D013577:Syndrome
chemical_list: D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C111952:OPHN1 protein, human; D010750:Phosphoproteins