Dataset Information

Intragenic MBD5 familial deletion variant does not negatively impact MBD5 mRNA expression.

ABSTRACT: 2q23.1 deletion syndrome is characterized by intellectual disability, speech impairment, seizures, disturbed sleep pattern, behavioral problems, and hypotonia. Core features of this syndrome are due to haploinsufficiency of MBD5. Deletions that include coding and noncoding exons show reduced MBD5 mRNA expression. We report a patient with a neurological and behavioral phenotype similar to 2q23.1 deletion syndrome with an inherited intronic deletion in the 5-prime untranslated region of MBD5. Our data show that this patient has normal MBD5 mRNA expression; therefore, this deletion is likely not causative for 2q23.1 deletion syndrome. Overall, it is important to validate intronic deletions for pathogenicity.

SUBMITTER: Mullegama SV

PROVIDER: S-EPMC4243375 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Intragenic MBD5 familial deletion variant does not negatively impact MBD5 mRNA expression.

Mullegama Sureni V SV Elsea Sarah H SH

Molecular cytogenetics 20141119 1

2q23.1 deletion syndrome is characterized by intellectual disability, speech impairment, seizures, disturbed sleep pattern, behavioral problems, and hypotonia. Core features of this syndrome are due to haploinsufficiency of MBD5. Deletions that include coding and noncoding exons show reduced MBD5 mRNA expression. We report a patient with a neurological and behavioral phenotype similar to 2q23.1 deletion syndrome with an inherited intronic deletion in the 5-prime untranslated region of MBD5. Our ...[more]

PMID: 25426169

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Project description:BACKGROUND:Infantile spasms (IS) is a specific type of epileptic encephalopathy associated with severe developmental disabilities. Genetic factors are strongly implicated in IS, however, the exact genetic defects remain unknown in the majority of cases. Rare mutations in a single gene or in copy number variants (CNVs) have been implicated in IS of children in Western countries. The objective of this study was to dissect the role of copy number variations in Chinese children with infantile spasms. METHODS:We used the Agilent Human Genome CGH microarray 180 K for genome-wide detection of CNVs. Real-time qPCR was used to validate the CNVs. We performed genomic and medical annotations for individual CNVs to determine the pathogenicity of CNVs related to IS. RESULTS:We report herein the first genome-wide CNV analysis in children with IS, detecting a total of 14 CNVs in a cohort of 47 Chinese children with IS. Four CNVs (4/47?=?8.5%) (1q21.1 gain; 1q44, 2q31.1, and 17p13 loss) are considered to be pathogenic. The CNV loss at 17p13.3 contains PAFAH1B1 (LIS1), a causative gene for lissencephaly. Although the CNVs at 1q21.1, 1q44, and 2q23.1 have been previously implicated in a wide spectrum of clinical features including autism spectrum disorders (ASD) and generalized seizure, our study is the first report identifying them in individuals with a primary diagnosis of IS. The CNV loss in the 1q44 region contains HNRNPU, a strong candidate gene recently suggested in IS by the whole exome sequencing of children with IS. The CNV loss at 2q23.1 includes MBD5, a methyl-DNA binding protein that is a causative gene of ASD and a candidate gene for epileptic encephalopathy. We also report a distinct clinical presentation of IS, microcephaly, intellectual disability, and absent hallux in a case with the 2q23.1 deletion. CONCLUSION:Our findings strongly support the role of CNVs in infantile spasms and expand the clinical spectrum associate with 2q23.1 deletion. In particular, our study implicates the HNRNPU and MBD5 genes in Chinese children with IS. Our study also supports that the molecular mechanisms of infantile spasms appear conserved among different ethnic backgrounds.

Dataset Information

Intragenic MBD5 familial deletion variant does not negatively impact MBD5 mRNA expression.

Publications

Intragenic MBD5 familial deletion variant does not negatively impact MBD5 mRNA expression.

Similar Datasets

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