title: Mutations in the SALL1 putative transcription factor gene cause Townes-Brocks syndrome.
abstract: 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.
authors.affiliation: Institut für Humangenetik der Universität Göttingen, Germany. jkohlha@gwdg.de
authors.forename: J
authors.initials: J
authors.lastname: Kohlhase
authors.forename: A
authors.initials: A
authors.lastname: Wischermann
authors.forename: H
authors.initials: H
authors.lastname: Reichenbach
authors.forename: U
authors.initials: U
authors.lastname: Froster
authors.forename: W
authors.initials: W
authors.lastname: Engel
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D018076:DNA, Complementary; D004431:Ear, External / Q000002:abnormalities; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017689:Polydactyly / Q000235:genetics; D013577:Syndrome; D013933:Thumb / Q000002:abnormalities; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; C104146:SALL1 protein, human; C491254:Sall1 protein, mouse; D014157:Transcription Factors