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

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. By whole-exome sequencing, we ident...

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Bibliographic Details
Published in:Orphanet journal of rare diseases 2014-01, Vol.9 (1), p.12-12, Article 12
Main Authors: Abdel-Salam, Ghada, Thoenes, Michaela, Afifi, Hanan H, Körber, Friederike, Swan, Daniel, Bolz, Hanno Jörn
Format: Article
Language:English
Subjects:
Complications and side effects
Epilepsy
Epilepsy - genetics
Gene mutations
Genetic aspects
Growth
Humans
Infant
Medical research
Microcephaly - genetics
Mutation
Oxidoreductases - genetics
Physiological aspects
Rare diseases
Retinal degeneration
Retinal Degeneration - genetics
Risk factors
Tumor Suppressor Proteins - genetics
WW Domain-Containing Oxidoreductase
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Summary: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. 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. 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.
ISSN:1750-1172
1750-1172
DOI:10.1186/1750-1172-9-12