Dataset Information

Whole Xp Deletion in a Girl with Mental Retardation, Epilepsy, and Biochemical Features of OTC Deficiency.

ABSTRACT: Background: Females with a total or partial deletion of the short arm of the X chromosome have variable features of Turner syndrome, but mental retardation (MR) rarely occurs. The haploinsufficiency of deleted genes that escape X-inactivation may explain the occurrence of MR and autism. Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder and is inherited in an X-linked semi-dominant trait, and the OTC gene maps to Xp21. Methods: We report on a girl with MR, epilepsy and biochemical changes characteristic of OTC deficiency but no identifiable point mutation in the OTC gene. Standard G-banding cytogenetic analysis, whole genome karyotyping, and X-inactivation studies were performed to determine the genetic etiology of the OTC deficiency in the patient. Results: Cytogenetic analysis and molecular karyotyping using SNP array revealed a deletion of the whole short arm of the X chromosome (Xp22.33-p11.1). Inactivation studies also revealed a completely skewed X-inactivation. Conclusion: Our patient presented with MR, epilepsy, and some evidence of reduced OTC activity, but performed genetic studies gave no explanation for this phenotype. We hope that this case report contributes to the understanding of the underlying genetic factors of the manifestation of X-linked disorders in female patients.

SUBMITTER: Joost K

PROVIDER: S-EPMC3214962 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Whole Xp Deletion in a Girl with Mental Retardation, Epilepsy, and Biochemical Features of OTC Deficiency.

Joost K K Tammur P P Teek R R Zilina O O Peters M M Kreile M M Lace B B Zordania R R Talvik I I Ounap K K

Molecular syndromology 20110914 6

Background: Females with a total or partial deletion of the short arm of the X chromosome have variable features of Turner syndrome, but mental retardation (MR) rarely occurs. The haploinsufficiency of deleted genes that escape X-inactivation may explain the occurrence of MR and autism. Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder and is inherited in an X-linked semi-dominant trait, and the OTC gene maps to Xp21. Methods: We report on a girl with MR, epileps ...[more]

PMID: 22190902

Similar Datasets

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

Whole Xp Deletion in a Girl with Mental Retardation, Epilepsy, and Biochemical Features of OTC Deficiency.

Publications

Whole Xp Deletion in a Girl with Mental Retardation, Epilepsy, and Biochemical Features of OTC Deficiency.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets