PURPOSE: Heterozygous germline @entity2750 mutations are causative of @entity9658 ( @entity1491 ), but detection rates > 70% have rarely been reported. We aimed to define the causative mutations in individuals with @entity9658 without @entity2750 mutations. METHODS: We undertook exome sequencing on lymphocyte DNA from four unrelated individuals from families with @entity9658 with no @entity2750 mutations found by Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), or RNA analysis. RESULTS: A germline heterozygous nonsense mutation in @entity25181 was identified in one of four exomes. Sanger sequencing of @entity25181 in 23 additional @entity2750 -negative @entity9658 families identified a @entity25181 mutation in a second family. Copy-number analysis of @entity25181 by MLPA revealed a large heterozygous deletion in a third family. All three @entity25181 -positive families fulfilled diagnostic criteria for @entity9658 , although none had odontogenic jaw keratocysts. Each @entity25181 -positive family included a single case of @entity2946 , whereas only two (1.7%) of 115 individuals with @entity9658 and a @entity2750 mutation developed @entity2946 . CONCLUSION: We demonstrate convincing evidence that @entity25181 mutations can cause classical @entity9658 . Our study redefines the risk of @entity2946 in @entity9658 , dependent on the underlying causative gene. Previous reports have found a 5% risk of @entity2946 in @entity9658 . We found a < 2% risk in @entity2750 mutation-positive individuals, with a risk up to 20* higher in @entity25181 mutation-positive individuals. Our data suggest childhood brain magnetic resonance imaging surveillance is justified in @entity25181 -related, but not @entity2750 -related, @entity9658 .

Germline Mutations in @entity25181 Cause Gorlin Syndrome-Associated XXXX and Redefine the Risk Associated With @entity2750 Mutations.

@entity9658 :: ('MESH:D001478', 'Disease') :: ['Gorlin syndrome'] @entity2750 :: ('5727', 'Gene') :: ['PTCH1'] @entity2946 :: ('MESH:D008527', 'Disease') :: ['medulloblastoma'] @entity1491 :: ('MESH:D002280', 'Disease') :: ['naevoid basal cell carcinoma'] @entity25181 :: ('51684', 'Gene') :: ['SUFU']
@entity2946 :: (MESH:D008527,Disease) :: ['Childhood Medulloblastoma']
