Association between @entity421 and deleterious mutations in the XXXX gene in @entity2641 .

@entity1 @entity25767 @entity1910 @entity5 @entity421 @entity74 @entity2641 @entity1141
BACKGROUND: @entity2641 ( @entity2641 ) is an @entity74 associated with an increased predisposition to @entity421 . @entity1 with @entity2641 typically present with a characteristic @entity1910 ( @entity2641 ), small stature, and @entity1141 . Mutations in the @entity25767 gene, which encodes a RecQ DNA helicase, have been reported in a few @entity2641 @entity1 . We examined whether a predisposition to developing @entity421 among an international cohort of @entity2641 @entity1 was associated with a distinctive pattern of mutations in the @entity25767 gene. METHODS: We obtained clinical information about and biologic samples from 33 @entity2641 @entity1 (age range = 1-30 years). Eleven @entity1 were diagnosed with @entity421 . All 21 exons and 13 short introns of the @entity25767 gene were sequenced from the genomic DNA of all subjects. Kaplan-Meier survival analysis was used to estimate the incidence of @entity421 among @entity1 with and without mutations predicted to produce a truncated @entity25767 protein. RESULTS: Twenty-three @entity2641 @entity1 , including all 11 @entity421 @entity1 , carried at least one of 19 truncating mutations in their @entity25767 genes. The incidence of @entity421 was 0.00 per year in truncating mutation-negative @entity1 (100 @entity1 -years of observation) and 0.05 per year in truncating mutation-positive @entity1 (230 @entity1 -years of observation) (P =.037; two-sided log-rank test). CONCLUSIONS: Mutations predicted to result in the loss of @entity25767 protein function occurred in approximately two-thirds of @entity2641 @entity1 and are associated with risk of @entity421 . Molecular diagnosis has the potential to identify those @entity1 with @entity2641 who are at high risk of this @entity5 .
