The supposed tumor suppressor gene WWOX is mutated in an early lethal microcephaly syndrome with epilepsy, growth retardation and retinal degeneration
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- 作者：Ghada Abdel-Salam (1)
Michaela Thoenes (2)
Hanan H Afifi (1)
Friederike K?rber (3)
Daniel Swan (4)
Hanno J?rn Bolz (2) (5) - 关键词：WWOX ; Tumor suppressor gene ; Microcephaly ; Epilepsy ; Retinal degeneration ; Nonsense mutation ; Whole ; exome sequencing
- 刊名：Orphanet Journal of Rare Diseases
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：9
- 期：1
- 全文大小：323 KB
- 作者单位：Ghada Abdel-Salam (1)
Michaela Thoenes (2)
Hanan H Afifi (1)
Friederike K?rber (3)
Daniel Swan (4)
Hanno J?rn Bolz (2) (5)
1. Department of Clinical Genetics, National Research Centre, Cairo, Egypt
2. Institute of Human Genetics, University Hospital of Cologne, Cologne, Germany
3. Department of Radiology, University of Cologne, Cologne, Germany
4. Computational Biology Group, Oxford Gene Technology, Oxford, OX5 1PF, UK
5. Center for Human Genetics, Bioscientia, Ingelheim, Germany - ISSN：1750-1172
文摘
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.