title: Molecular analysis of SALL1 mutations in Townes-Brocks syndrome.
abstract: Townes-Brocks syndrome (TBS) is an autosomal dominantly inherited malformation syndrome characterized by anal, renal, limb, and ear anomalies. Recently, we showed that mutations in the putative zinc finger transcription factor gene SALL1 cause TBS. To determine the spectrum of SALL1 mutations and to investigate the genotype-phenotype correlations in TBS, we examined 23 additional families with TBS or similar phenotypes for SALL1 mutations. In 9 of these families mutations were identified. None of the mutations has previously been described. Two of these mutations are nonsense mutations, one of which occurred in three unrelated families. Five of the mutations are short deletions. All of the mutations are located 5' of the first double zinc finger (DZF) encoding region and are therefore predicted to result in putative prematurely terminated proteins lacking all DZF domains. This suggests that only SALL1 mutations that remove the DZF domains result in TBS. We also present evidence that in rare cases SALL1 mutations can lead to phenotypes similar to Goldenhar syndrome. However, phenotypic differences in TBS do not seem to depend on the site of mutation.
authors.affiliation: Institute for Human Genetics, University of Göttingen, Gosslerstr. 12d, D-37073Göttingen, Germany. jkohlha@gwdg.de
authors.forename: J
authors.initials: J
authors.lastname: Kohlhase
authors.forename: P E
authors.initials: PE
authors.lastname: Taschner
authors.forename: P
authors.initials: P
authors.lastname: Burfeind
authors.forename: B
authors.initials: B
authors.lastname: Pasche
authors.forename: B
authors.initials: B
authors.lastname: Newman
authors.forename: C
authors.initials: C
authors.lastname: Blanck
authors.forename: M H
authors.initials: MH
authors.lastname: Breuning
authors.forename: L P
authors.initials: LP
authors.lastname: ten Kate
authors.forename: P
authors.initials: P
authors.lastname: Maaswinkel-Mooy
authors.forename: B
authors.initials: B
authors.lastname: Mitulla
authors.forename: J
authors.initials: J
authors.lastname: Seidel
authors.forename: S J
authors.initials: SJ
authors.lastname: Kirkpatrick
authors.forename: R M
authors.initials: RM
authors.lastname: Pauli
authors.forename: D S
authors.initials: DS
authors.lastname: Wargowski
authors.forename: K
authors.initials: K
authors.lastname: Devriendt
authors.forename: W
authors.initials: W
authors.lastname: Proesmans
authors.forename: O
authors.initials: O
authors.lastname: Gabrielli
authors.forename: G V
authors.initials: GV
authors.lastname: Coppa
authors.forename: E
authors.initials: E
authors.lastname: Wesby-van Swaay
authors.forename: R C
authors.initials: RC
authors.lastname: Trembath
authors.forename: A A
authors.initials: AA
authors.lastname: Schinzel
authors.forename: W
authors.initials: W
authors.lastname: Reardon
authors.forename: E
authors.initials: E
authors.lastname: Seemanova
authors.forename: W
authors.initials: W
authors.lastname: Engel
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D001006:Anus, Imperforate / Q000235:genetics; D001483:Base Sequence; D003001:Cloning, Molecular; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*