PURPOSE: Mastermind-like domain containing 1 ( @entity29786 ) is a causative gene for the fetal development of male external genitalia. Almost 10% of @entity1 with both severe and non-severe @entity2650 exhibit mutations of @entity29786 . The aim of this work was to determine whether polymorphisms of @entity29786 are a genetic risk factor for @entity2650 . MATERIAL AND METHODS: This study included 150 @entity2650 with a range of severities and 150 controls. Direct sequencing of the @entity29786 coding exons and their flanking splice sites was performed. In silico secondary and tertiary structure prediction and accessibility of changed @entity1522 were evaluated using JPred, Netsurf and PHYRE software. Functional studies of the transactivation of haplotypes on @entity23196 promoter were performed in  vitro using cDNAs of missense variants of @entity29786 . RESULTS: The @entity46383 polymorphism was identified in 17/150 @entity1 and 12/150 controls (11.3% vs. 8.0%, p  =  0.32). The @entity70516 polymorphism was identified in 22/150 @entity1 and 12/150 controls (14.6% vs. 8.0%, p  =  0.068). The double polymorphism (S-S haplotype) was present in 16/150 @entity1 and 6/150 controls (10.6% vs. 4.0%, p  =  0.044, OR  =  2.87, CI from 1.09 to 7.55). The association of polymorphisms consistently revealed a modification in the structure prediction or @entity535 accessibility in all three in silico models. The @entity46383 , @entity70516 and @entity46383  +  @entity70516 proteins did not exhibit reduced transactivating activity on @entity23196 promoter. CONCLUSION: Polymorphisms of @entity29786 gene are frequent in @entity1 with @entity2650 . Although no change in transactivation was noted on @entity23196 promoter, the in silico studies and the significantly increased incidence of the S-S haplotype in hypospadiac @entity1 raise the hypothesis of a particular susceptibility conferred by these variants.

Polymorphisms of @entity29786 gene in XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity1522 :: ('CHEBI:33709', 'Chemical') :: ['amino acids'] @entity2650 :: ('MESH:D007021', 'Disease') :: ['hypospadias'] @entity535 :: ('CHEBI:33704', 'Chemical') :: ['amino acid'] @entity46383 :: ('p|SUB|P|286|S', 'ProteinMutation') :: ['p.P286S', 'P286S'] @entity23196 :: ('390992', 'Gene') :: ['Hes3'] @entity29786 :: ('10046', 'Gene') :: ['MAMLD1'] @entity70516 :: ('p|SUB|N|589|S', 'ProteinMutation') :: ['N589S', 'p.N589S']
@entity2650 :: (MESH:D007021,Disease) :: ['hypospadias']
