A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators

Hum Mol Genet. 1999 Jun;8(6):989-96. doi: 10.1093/hmg/8.6.989.


Deletion of the distal short arm of chromosome 9 (9p) has been reported in a number of cases to be associated with gonadal dysgenesis and XY sex reversal, suggesting that this region contains one or more genes required in two copies for normal testis development. Recent studies have greatly narrowed the interval containing this putative autosomal testis-determining gene(s) to the distal portion of 9p24.3. We previously identified DMRT1, a human gene with sequence similarity to genes that regulate the sexual development of nematodes and insects. These genes contain a novel DNA-binding domain, which we named the DM domain. DMRT1 maps to 9p24. 3 and in adults is expressed specifically in the testis. We have investigated the possible role of DM domain genes in 9p sex reversal. We identified a second DM domain gene, DMRT2, which also maps to 9p24.3. We found that point mutations in the coding region of DMRT1 and the DM domain of DMRT2 are not frequent in XY females. We showed by fluorescence in situ hybridization analysis that both genes are deleted in the smallest reported sex-reversing 9p deletion, suggesting that gonadal dysgenesis in 9p-deleted individuals might be due to combined hemizygosity of DMRT1 and DMRT2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Child, Preschool
  • Chromosome Mapping
  • Chromosomes, Human, Pair 9 / genetics*
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • DNA-Binding Proteins / metabolism
  • Disorders of Sex Development
  • Female
  • Genes / genetics*
  • Gonadal Dysgenesis, 46,XY / genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Molecular Sequence Data
  • Point Mutation
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Sequence Analysis, DNA
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Sex Determination Processes*
  • Sex Differentiation / genetics
  • Testis / embryology
  • Testis / growth & development*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • DMRT1 protein
  • DMRT2 protein, human
  • DNA, Complementary
  • DNA-Binding Proteins
  • Protein Isoforms
  • Transcription Factors

Associated data

  • GENBANK/AF130728
  • GENBANK/AF130729