title: Translocation breakpoint maps 5 kb 3' from TWIST in a patient affected with Saethre-Chotzen syndrome.
abstract: Saethre-Chotzen syndrome, a common autosomal dominant craniosynostosis in humans, is characterized by brachydactyly, soft tissue syndactyly and facial dysmorphism including ptosis, facial asymmetry, and prominent ear crura. Previously, we identified a yeast artificial chromosome that encompassed the breakpoint of an apparently balanced t(6;7) (q16.2;p15.3) translocation associated with a mild form of Saethre-Chotzen syndrome. We now describe, at the DNA sequence level, the region on chromosome 7 affected by this translocation event. The rearrangement occurred approximately 5 kb 3' of the human TWIST locus and deleted 518 bp of chromosome 7. The TWIST gene codes for a transcription factor containing a basic helix-loop-helix (b-HLH) motif and has recently been described as a candidate gene for Saethre-Chotzen syndrome, based on the detection of mutations within the coding region. Potential exon sequences flanking the chromosome 7 translocation breakpoint did not hit known genes in database searches. The chromosome rearrangement downstream of TWIST is compatible with the notion that this is a Saethre-Chotzen syndrome gene and implies loss of function of one allele by a positional effect as a possible mechanism of mutation to evoke the syndrome.
authors.affiliation: Phillips-Universität Marburg, Medizinisches Zentrum für Humangenetik,Germany.
authors.forename: I
authors.initials: I
authors.lastname: Krebs
authors.forename: I
authors.initials: I
authors.lastname: Weis
authors.forename: M
authors.initials: M
authors.lastname: Hudler
authors.forename: J M
authors.initials: JM
authors.lastname: Rommens
authors.forename: H
authors.initials: H
authors.lastname: Roth
authors.forename: S W
authors.initials: SW
authors.lastname: Scherer
authors.forename: L C
authors.initials: LC
authors.lastname: Tsui
authors.forename: E M
authors.initials: EM
authors.lastname: Füchtbauer
authors.forename: K H
authors.initials: KH
authors.lastname: Grzeschik
authors.forename: K
authors.initials: K
authors.lastname: Tsuji
authors.forename: J
authors.initials: J
authors.lastname: Kunz
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics*; D001483:Base Sequence; D019457:Chromosome Breakage; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D003360:Cosmids / Q000235:genetics; D018076:DNA, Complementary; D015894:Genome, Human; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D051879:Twist-Related Protein 1
chemical_list: D018076:DNA, Complementary; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1