The supposed tumor suppressor gene WWOX is mutated in an early lethal microcephaly syndrome with epilepsy, growth retardation and retinal degeneration

Orphanet Journal of Rare Diseases

Hanno Jörn Bolz⁵  Daniel Swan³  Friederike Körber²  Hanan H Afifi⁴  Michaela Thoenes¹  Ghada Abdel-Salam⁴ 

[1] Institute of Human Genetics, University Hospital of Cologne, Cologne, Germany;Department of Radiology, University of Cologne, Cologne, Germany;Computational Biology Group, Oxford Gene Technology, Oxford, OX5 1PF, UK;Department of Clinical Genetics, National Research Centre, Cairo, Egypt;Center for Human Genetics, Bioscientia, Ingelheim, Germany

关键词: Whole-exome sequencing;    Nonsense mutation;    Retinal degeneration;    Epilepsy;    Microcephaly;    Tumor suppressor gene;    WWOX;   

Others  :  863270
DOI  :  10.1186/1750-1172-9-12

 received in 2013-09-25, accepted in 2014-01-22,  发布年份 2014

【 摘 要 】

Background

WWOX, encoding WW domain-containing oxidoreductase, spans FRA16D, the second most common chromosomal fragile site frequently altered in cancers. It is therefore considered a tumor suppressor gene, but its direct implication in cancerogenesis remains controversial.

Methods and results

By whole-exome sequencing, we identified a homozygous WWOX nonsense mutation, p.Arg54*, in a girl from a consanguineous family with a severe syndrome of growth retardation, microcephaly, epileptic seizures, retinopathy and early death, a phenotype highly similar to the abormalities reported in lde/lde rats with a spontaneous functional null mutation of Wwox. As in rats, no tumors were observed in the patient or heterozygous mutation carriers.

Conclusions

Our finding, a homozygous loss-of-function germline mutation in WWOX in a patient with a lethal autosomal recessive syndrome, supports an alternative role of WWOX and indicates its importance for human viability.

【 授权许可】

   
2014 Abdel-Salam et al.; licensee BioMed Central Ltd.

【 图 表 】

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