PMID- 12454025
OWN - NLM
STAT- MEDLINE
DCOM- 20021212
LR  - 20220129
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 43
IP  - 12
DP  - 2002 Dec
TI  - A peptidase gene in chromosome 8q is disrupted by a balanced translocation in a 
      duane syndrome patient.
PG  - 3609-12
AB  - PURPOSE: 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.
FAU - Pizzuti, Antonio
AU  - Pizzuti A
AD  - Department of Experimental Medicine and Pathology, University of Rome La 
      Sapienza, Italy. antpizzuti@libero.it
FAU - Calabrese, Giuseppe
AU  - Calabrese G
FAU - Bozzali, Maura
AU  - Bozzali M
FAU - Telvi, Louise
AU  - Telvi L
FAU - Morizio, Elisena
AU  - Morizio E
FAU - Guida, Valentina
AU  - Guida V
FAU - Gatta, Valentina
AU  - Gatta V
FAU - Stuppia, Liborio
AU  - Stuppia L
FAU - Ion, Alexandra
AU  - Ion A
FAU - Palka, Giandomenico
AU  - Palka G
FAU - Dallapiccola, Bruno
AU  - Dallapiccola B
LA  - eng
GR  - E.0689/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (RNA, Messenger)
RN  - EC 3.4.- (Carboxypeptidases)
RN  - EC 3.4.17.1 (Carboxypeptidases A)
SB  - IM
MH  - Adult
MH  - Alternative Splicing/genetics
MH  - Amino Acid Sequence
MH  - Blotting, Northern
MH  - Carboxypeptidases/*genetics
MH  - Carboxypeptidases A
MH  - Chromosome Breakage/*genetics
MH  - Chromosomes, Artificial, Yeast
MH  - Chromosomes, Human, Pair 6/genetics
MH  - Chromosomes, Human, Pair 8/*genetics
MH  - Duane Retraction Syndrome/enzymology/*genetics
MH  - Expressed Sequence Tags
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Molecular Sequence Data
MH  - Point Mutation
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/genetics
MH  - Sequence Analysis, DNA
MH  - Sequence Homology, Amino Acid
MH  - *Translocation, Genetic
EDAT- 2002/11/28 04:00
MHDA- 2002/12/13 04:00
CRDT- 2002/11/28 04:00
PHST- 2002/11/28 04:00 [pubmed]
PHST- 2002/12/13 04:00 [medline]
PHST- 2002/11/28 04:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2002 Dec;43(12):3609-12.