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


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.
Ghada
G
Abdel-Salam
Michaela
M
Thoenes
Hanan H
HH
Afifi
Friederike
F
Körber
Daniel
D
Swan
Institute of Human Genetics, University Hospital of Cologne, Cologne, Germany. hanno.bolz@uk-koeln.de.
Hanno Jörn
HJ
Bolz
D004827:Epilepsy / Q000235:genetics*; D006801:Humans; D007223:Infant; D008831:Microcephaly / Q000235:genetics*; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics; D012162:Retinal Degeneration / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000074584:WW Domain-Containing Oxidoreductase
D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human