A Novel Whole Exon Deletion in WWOX Gene Causes Early Epilepsy, Intellectual Disability and Optic Atrophy

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• 作者：Salma Ben-Salem ; Aisha M. Al-Shamsi ; Anne John…
• 关键词：Whole ; chromosomal microarray ; WWOX ; Microdeletion ; Microcephaly ; ID
• 刊名：Journal of Molecular Neuroscience
• 出版年：2015
• 出版时间：May 2015
• 年：2015
• 卷：56
• 期：1
• 页码：17-23
• 全文大小：2,904 KB
• 参考文献：1. Abdel-Salam, G, Thoenes, M, Afifi, HH, K?rber, F, Swan, D, Bolz, HJ (2014) The supposed tumor suppressor gene WWOX is mutated in an early lethal microcephaly syndrome with epilepsy, growth retardation and retinal degeneration. Orphanet J Rare Dis 9: pp. 12 CrossRef
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• 刊物主题：Neurosciences; Neurochemistry; Cell Biology; Proteomics; Neurology;
• 出版者：Springer US
• ISSN：1559-1166

文摘

Recent studies have implicated the WW domain-containing oxidoreductase encoding gene (WWOX) in a severe form of autosomal recessive neurological disorder. This condition showed an overlapping spectrum of clinical features including spinocerebellar ataxia associated with generalized seizures and delayed psychomotor development to growth retardation, spasticity, and microcephaly. We evaluated a child from a consanguineous Emirati family that presented at birth with growth retardation, microcephaly, epileptic seizures, and later developed spasticity and delayed psychomotor development. Screening for deletions and duplications using whole-chromosomal microarray analysis identified a novel homozygous microdeletion encompassing exon 5 of the WWOX gene. Analysis of parental DNA indicated that this deletion was inherited from both parents and lies within a large region of homozygosity. Sanger sequencing of the cDNA showed that the deletion resulted in exon 5 skipping leading to a frame-shift and creating a premature stop codon at amino acid position 212. Quantification of mRNA revealed striking low level of WWOX expression in the child and moderate level of expression in the mother compared to a healthy control. To the best of our knowledge, this is the first homozygous germline structural variation in WWOX gene resulting in truncated transcripts that were presumably?subject to NMD pathway. Our findings extend the clinical and genetic spectrum of WWOX mutations and support a crucial role of this gene in neurological development.