Mutations in the SALL1 putative transcription factor gene cause Townes-Brocks syndrome

Nat Genet. 1998 Jan;18(1):81-3. doi: 10.1038/ng0198-81.


Townes-Brocks syndrome (TBS, OMIM #107480) is a rare autosomal-dominant malformation syndrome with a combination of anal, renal, limb and ear anomalies. Cytogenetic findings suggested that the gene mutated in TBS maps to chromosome 16q12.1, where SALL1 (previously known as HSAL1), a human homologue of spalt (sal), is located. SAL is a developmental regulator in Drosophila melanogaster and is conserved throughout evolution. No phenotype has yet been attributed to mutations in vertebrate sal-like genes. The expression patterns of sal-like genes in mouse, Xenopus and the fish Medaka, and the finding that Medaka sal is regulated by Sonic hedgehog (Shh; ref. 11), prompted us to examine SALL1 as a TBS candidate gene. Here we demonstrate that SALL1 mutations cause TBS in a family with vertical transmission of TBS and in an unrelated family with a sporadic case of TBS. Both mutations are predicted to result in a prematurely terminated SALL1 protein lacking all putative DNA binding domains. TBS therefore represents another human developmental disorder caused by mutations in a putative C2H2 zinc-finger transcription factor.

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Amino Acid Sequence
  • Base Sequence
  • DNA, Complementary
  • Ear, External / abnormalities
  • Female
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Polydactyly / genetics
  • Syndrome
  • Thumb / abnormalities
  • Transcription Factors / genetics*
  • Zinc Fingers / genetics*


  • DNA, Complementary
  • SALL1 protein, human
  • Sall1 protein, mouse
  • Transcription Factors

Associated data

  • GENBANK/X98833