Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Oligophrenin 1 (OPHN1) gene mutation causes syndromic X-linked mental retardation with epilepsy, rostral ventricular enlargement and cerebellar hypoplasia. 1280 98

We report on a patient with mental retardation, seizures and tall stature with advanced bone age in whom a de novo apparently balanced chromosomal rearrangement 46,XX,t(X;9)(q12;p13.3) was identified. Using array CGH on flow-sorted derivative chromosomes (array painting) and subsequent FISH and qPCR analysis, we mapped and sequenced both breakpoints. The Xq12 breakpoint was located within the gene coding for oligophrenin 1 (OPHN1) whereas the 9p13.3 breakpoint was assigned to a non-coding segment within a gene dense region. Disruption of OPHN1 by the Xq12 breakpoint was considered the major cause of the abnormal phenotype observed in the proband.
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PMID:Report of a female patient with mental retardation and tall stature due to a chromosomal rearrangement disrupting the OPHN1 gene on Xq12. 1784 70

X-linked mental retardation (XLMR) is notably a heterogeneous condition and often poses a diagnostic challenge. The oligophrenin 1 gene (OPHN1) is a protein with a Rho-GTPase-activating domain required in the regulation of the G-protein cycle. Mutations in the OPHN1 cause XLMR with cerebellar hypoplasia and distinctive facial appearance. We report a large Saudi family of four boys and one girl affected with XLMR. The boys had moderate MR, seizure disorder, facial dysmorphism, and cerebellar vermis hypoplasia. The girl had mild MR, seizures, and mild cerebellar hypoplasia. A novel deletion of at least exons 7-15 was identified by polymerase chain reaction analysis and multiple ligation probe amplification of the OPHN1 gene. The array comparative genomic hybridization further delineated approximately 68 kb deletion of the 7-15 exons and nearly half of intron 15. In addition, the X-inactivation confirmed random pattern in the girl. Although the affected boys have remarkably similar phenotype, there was some variability in the severity of the seizure disorder and the cerebellar hypoplasia. The report confirms the previous findings that carrier females may be symptomatic.
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PMID:Novel intragenic deletion in OPHN1 in a family causing XLMR with cerebellar hypoplasia and distinctive facial appearance. 2052 89

Mutations in the oligophrenin 1 gene (OPHN1) have been identified in patients with X-linked intellectual disability (XLID) associated with cerebellar hypoplasia and ventriculomegaly, suggesting it could be a recognizable syndromic intellectual disability (ID). Affected individuals share additional clinical features including speech delay, seizures, strabismus, behavioral difficulties, and slight facial dysmorphism. OPHN1 is located in Xq12 and encodes a Rho-GTPase-activating protein involved in the regulation of the G-protein cycle. Rho protein members play an important role in dendritic growth and in plasticity of excitatory synapses. Here we report on 17 individuals from four unrelated families affected by mild to severe intellectual disability due to OPHN1 mutations without cerebellar anomaly on brain MRI. We describe clinical, genetic and neuroimaging data of affected patients. Among the identified OPHN1 mutations, we report for the first time a missense mutation occurring in a mosaic state. We discuss the intrafamilial clinical variability of the disease and compare our patients with those previously reported. We emphasize the power of next generation techniques (X-exome sequencing, whole-exome sequencing and targeted multi-gene panel) to expand the phenotypic and mutational spectrum of OPHN1-related ID.
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PMID:Expanding the phenotypic spectrum associated with OPHN1 mutations: Report of 17 individuals with intellectual disability but no cerebellar hypoplasia. 2951 Feb 40