Mutational study of the MAMLD1-gene in hypospadias

Eur J Med Genet. 2010 May-Jun;53(3):122-6. doi: 10.1016/j.ejmg.2010.03.005. Epub 2010 Mar 25.

Abstract

Hypospadias, when the urethral opening is situated on the ventral side of the penis, is a common genital malformation in boys and is partly caused by genetic factors. Mutations in the Mastermind-like domain containing 1 (MAMLD1 or CXorf6) gene have been reported in hypospadias cases. We have performed direct sequencing of the MAMLD1 gene in 99 sporadic hypospadias cases to further elucidate the role of this gene in hypospadias. Five non-synonymous mutations, one synonymous and one non-coding mutation were found. Of those, p.P286S, p.V432A, p.N589S and p.531ins3Q have previously been reported and are indicated in our study as polymorphisms. One new mutation, p.Q529K, was found in one patient with severe hypospadias and it was predicted to affect the splicing process. In our material we also found a weak association between hypospadias and the p.N589S polymorphism and in a haplotype analysis the rare alleles of p.P286S and p.N589S were more common in cases than in controls.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Aneuploidy
  • DNA Mutational Analysis / methods*
  • DNA-Binding Proteins / genetics*
  • Haplotypes
  • Humans
  • Hypospadias / genetics*
  • Introns
  • Male
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • MAMLD1 protein, human
  • Nuclear Proteins
  • Transcription Factors