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Orphanet J Rare Dis. 2014 Jan 23;9:12. doi: 10.1186/1750-1172-9-12.

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

Author information

1
Institute of Human Genetics, University Hospital of Cologne, Cologne, Germany. hanno.bolz@uk-koeln.de.

Abstract

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.

PMID:
24456803
PMCID:
PMC3918143
DOI:
10.1186/1750-1172-9-12
[Indexed for MEDLINE]
Free PMC Article

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