Dataset Information

A novel PCDH19 missense mutation, c.812G>A (p.Gly271Asp), identified using whole-exome sequencing in a Chinese family with epilepsy female restricted mental retardation syndrome.

ABSTRACT: BACKGROUND:Epilepsy limited to females with mental retardation (EFMR) is a rare type of epilepsy with an X-linked mode of inheritance, which affect heterozygous females while the males are not affected. Mutations within the protocadherin 19 (PCDH19) gene have been identified as the direct cause of EFMR. The phenotype of EFMR is characterized by seizure onset in infancy with or without cognitive impairment, intellectual disturbances, and autistic features. METHODS:Whole-exome sequencing (WES) was performed in the proband to identify the underlying genetic mutations. The candidate genes were confirmed by Sanger sequencing following PCR amplification. In silico?analyses were conducted to predict the effect of the novel missense mutation on the function of PCDH19 protein. RESULTS:We identified three female patients in a family with a novel missense mutation in PCDH19, c.812G>A (p. (Gly271Asp)). The patients III-1 and III-2 presented with more severe clinical phenotypes and an earlier age of onset (6 and 11 months, respectively), intellectual disability, and movement disorders. By contrast, patient II-4 has a later age of onset (23 months), and there was no relapse of seizures without antiepileptic treatment after the age of six. In silico?analyses?showed?that p. (Gly271Asp)?in the PCDH19?affects?a?highly?conserved residue. CONCLUSIONS:Our results indicated that patients with the same PCDH19 mutation in a family may show intrafamilial phenotypic variability. Givening the mother of the proband was 18 weeks pregnant and intends to have a prenatal diagnosis, the more reasonable and less harmful strategies for prenatal diagnosis could be chosen based on the results of noninvasive prenatal testing and genetic testing.

SUBMITTER: Zhao X

PROVIDER: S-EPMC7284031 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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A novel PCDH19 missense mutation, c.812G>A (p.Gly271Asp), identified using whole-exome sequencing in a Chinese family with epilepsy female restricted mental retardation syndrome.

Zhao Xuechao X Wang Yanhong Y Mei Shiyue S Kong Xiangdong X

Molecular genetics & genomic medicine 20200421 6

<h4>Background</h4>Epilepsy limited to females with mental retardation (EFMR) is a rare type of epilepsy with an X-linked mode of inheritance, which affect heterozygous females while the males are not affected. Mutations within the protocadherin 19 (PCDH19) gene have been identified as the direct cause of EFMR. The phenotype of EFMR is characterized by seizure onset in infancy with or without cognitive impairment, intellectual disturbances, and autistic features.<h4>Methods</h4>Whole-exome seque ...[more]

PMID: 32314541

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Project description:RATIONALE:Epilepsy with mental retardation limited to females (EFMR) is a rare type of X-linked epilepsy disorder, affecting heterozygous females disproportionately. The pathogenesis of EFMR has been identified as mutations in the protocadherin 19 (PCDH19) gene. To data, more than 60 different mutations in PCDH19 have been identified. Most of them are located at exon 1, but we describe a novel deletion mutation c.2468delT at exon 3 of PCDH19. PATIENT CONCERNS:The patient was an 11-year-old girl with onset of seizures at the age of 18 months and followed by progressive intellectual disability (ID) later. DIAGNOSIS:The girl was diagnosed as EFMR when a novel deletion mutation c.2468delT at exon 3 of PCDH19 was found. The deletion mutation c.2468delT was predicted to have caused a frameshift mutation of amino acid at position 823 (p.L823fs). There was no family history of seizures or ID. Her father was asymptomatic, but the mutation screening shows that he had a hemizygous mutation c.2468delT at the same site of PCDH19. The secondary structure of PCDH19 (wide type) showed that the sequences undergoing frameshift mutations were located in the cytoplasm and contain 9 phosphorylation sites. The p.L823fs mutation caused a totally different amino sequence after position of 823, thereby resulting in the disappearance of phosphorylation sites. The frameshift mutation of amino acid at position 823 might affect its binding capability with GABAA receptor and results in migration and morphological maturation of hippocampal neurons. INTERVENTIONS:The patient has received antiepileptic treatments, including sodium valproate, carbamazepine, levetiracetam, topiramate and clonazepam et al. OUTCOMES:: The antiepileptic treatment effects were limited. LESSONS:This case report describes a novel PCDH19 gene mutation (c.2468delT) at exon 3 in a girl suffering from EFMR. The deletion mutation was predicted to cause a frameshift mutation-p.L823fs, which is highly conserved across different species.

Dataset Information

A novel PCDH19 missense mutation, c.812G>A (p.Gly271Asp), identified using whole-exome sequencing in a Chinese family with epilepsy female restricted mental retardation syndrome.

Publications

A novel PCDH19 missense mutation, c.812G>A (p.Gly271Asp), identified using whole-exome sequencing in a Chinese family with epilepsy female restricted mental retardation syndrome.

Similar Datasets

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