title: A peptidase gene in chromosome 8q is disrupted by a balanced translocation in a duane syndrome patient.
abstract: OBJECTIVE
  To identify the gene disrupted by a de novo reciprocal balanced translocation t(6;8)(q26;q13) in a patient with Duane retraction syndrome (DURS). The break point in chromosome arm 8q is positioned within the DURS1 critical region.
  
  
  METHODS
  Fluorescence in situ hybridization (FISH) analysis using cosmid and BAC clones covering the DURS1 locus was performed to define the break point position and its relationship with expressed sequence tags (ESTs) in the region. Once the interrupted gene was identified, the full-length cDNA was sequenced and the genomic organization defined. Eighteen patients with sporadic DURS without cytogenetic abnormalities involving the DURS1 region were screened for point mutations in the candidate DURS1 gene.
  
  
  RESULTS
  A carboxypeptidase gene (CPAH) was directly interrupted between the first and second exons in a patient with DURS who carried a de novo reciprocal balanced translocation t(6;8)(q26;q13) involving the DURS1 region on chromosome arm 8q13. The gene was transcribed in at least two alternative mRNA forms, with different start and stop codons.
  
  
  CONCLUSIONS
  The CPAH gene was interrupted in a patient with DURS carrying a translocation break point in the DURS1 region on chromosome 8q13. CPAH is therefore a likely candidate for this abnormality, even if the possibility that other genes are involved, either by direct effects on transcription units present in the first CPAH intron or by position effects, cannot be ruled out. Functional studies of the influence of this gene on the morphogenesis of eye muscles and their innervation may clarify this question.
authors.affiliation: Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Italy. antpizzuti@libero.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Pizzuti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Calabrese
authors.forename: Maura
authors.initials: M
authors.lastname: Bozzali
authors.forename: Louise
authors.initials: L
authors.lastname: Telvi
authors.forename: Elisena
authors.initials: E
authors.lastname: Morizio
authors.forename: Valentina
authors.initials: V
authors.lastname: Guida
authors.forename: Valentina
authors.initials: V
authors.lastname: Gatta
authors.forename: Liborio
authors.initials: L
authors.lastname: Stuppia
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ion
authors.forename: Giandomenico
authors.initials: G
authors.lastname: Palka
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D000328:Adult; D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D015152:Blotting, Northern; D002268:Carboxypeptidases / Q000235:genetics*; D043422:Carboxypeptidases A; D019457:Chromosome Breakage / Q000235:genetics*; D018244:Chromosomes, Artificial, Yeast; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004370:Duane Retraction Syndrome / Q000201:enzymology / Q000235:genetics*; D020224:Expressed Sequence Tags; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014178:Translocation, Genetic
chemical_list: D012333:RNA, Messenger; D002268:Carboxypeptidases; D043422:Carboxypeptidases A