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)

Progressive encephalopathy with oedema, hypsarrhythmia and optic atrophy (PEHO) syndrome is a rare Mendelian phenotype comprising severe retardation, early onset epileptic seizures, optic nerve/cerebellar atrophy, pedal oedema, and early death. Atypical cases are often known as PEHO-like, and there is an overlap with 'early infantile epileptic encephalopathy'. PEHO is considered to be recessive, but surprisingly since initial description in 1991, no causative recessive gene(s) have been described. Hence, we report a multiplex consanguineous family with the PEHO phenotype where affected individuals had a homozygous frame-shift deletion in CCDC88A (c.2313delT, p.Leu772*ter). Analysis of cDNA extracted from patient lymphocytes unexpectedly failed to show non-sense mediated decay, and we demonstrate that the mutation produces a truncated protein lacking the crucial C-terminal half of CCDC88A (girdin). To further investigate the possible role of CCDC88A in human neurodevelopment we re-examined the behaviour and neuroanatomy of Ccdc88a knockout pups. These mice had mesial-temporal lobe epilepsy, microcephaly and corpus callosum deficiency, and by postnatal Day 21, microcephaly; the mice died at an early age. As the mouse knockout phenotype mimics the human PEHO phenotype this suggests that loss of CCDC88A is a cause of the PEHO phenotype, and that CCDC88A is essential for multiple aspects of normal human neurodevelopment.
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PMID:CCDC88A mutations cause PEHO-like syndrome in humans and mouse. 2691 97

Progressive encephalopathy, edema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an unusual Mendelian phenotype of unidentified origin that causes profound intellectual disability, optic nerve/cerebellar atrophy, epileptic seizures, developmental progress, pedal edema, and early death. Uncharacteristic affected individuals are often classified as having PEHO-like syndrome, although they may be misdiagnosed as having epileptic encephalopathy, a potential result of early birth. In this study, we report a consanguineous Saudi family with a novel homozygous nonsense mutation of the CCDC88A gene causing PEHO-like syndrome. The children were suffering from developmental delay, epilepsy, mental disability, optic nerve/cerebellar atrophy, and pedal edema. Whole exome sequencing was conducted for the members of the family who have the disorder to study the novel mutation. Whole exome sequencing data analysis, confirmed by subsequent Sanger sequencing validation, identified a novel homozygous nonsense mutation c. 1292G > A, which was caused by p.Trp431* stop gain. This mutation was ruled out in 100 unrelated healthy controls. The nonsense homozygous mutation detected in this study has not yet been reported as pathogenic in the literature or various databases. In conclusion, a complete loss of protein function due to premature stop gain was caused by a mutation in exon 12 of CCDC88A. This loss may lead to PEHO phenotype. CCDC88A gene may therefore play an important and critical role for multiple aspects of normal human neurodevelopment.
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PMID:A novel homozygous nonsense mutation in CCDC88A gene cause PEHO-like syndrome in consanguineous Saudi family. 3039 57