PMID- 17534888
OWN - NLM
STAT- MEDLINE
DCOM- 20070827
LR  - 20200930
IS  - 1552-4825 (Print)
IS  - 1552-4825 (Linking)
VI  - 143A
IP  - 14
DP  - 2007 Jul 15
TI  - Methylthioadenosine phosphorylase (MTAP) in hearing: gene disruption by 
      chromosomal rearrangement in a hearing impaired individual and model organism 
      analysis.
PG  - 1630-9
AB  - Genes with a role in the auditory system have been mapped by genetic linkage 
      analysis of families with heritable deafness and then cloned through positional 
      candidate gene approaches. Another positional method for gene discovery is to 
      ascertain deaf individuals with balanced chromosomal translocations and identify 
      disrupted or disregulated genes at the site(s) of rearrangement. We report herein 
      the use of fluorescence in situ hybridization (FISH) to map the breakpoint 
      regions on each derivative chromosome of a de novo apparently balanced 
      translocation, t(8;9)(q12.1;p21.3)dn, in a deaf individual. Chromosomal 
      breakpoints were assigned initially by GTG-banding of metaphase chromosomes and 
      then BAC probes chosen to map precisely the breakpoints by FISH experiments. To 
      facilitate cloning of the breakpoint sequences, further refinement of the 
      breakpoints was performed by FISH experiments using PCR products and by Southern 
      blot analysis. The chromosome 9 breakpoint disrupts methylthioadenosine 
      phosphorylase (MTAP); no known or predicted genes are present at the chromosome 8 
      breakpoint. Disruption of MTAP is hypothesized to lead to deafness due to the 
      role of MTAP in metabolizing an inhibitor of polyamine synthesis. Drosophila 
      deficient for the MTAP ortholog, CG4,802, were created and their hearing 
      assessed; no hearing loss phenotype was observed. A knockout mouse model for MTAP 
      deficiency was also created and no significant hearing loss was detected in 
      heterozygotes for Mtap. Homozygous Mtap-deficient mice were embryonic lethal.
CI  - (c) 2007 Wiley-Liss, Inc
FAU - Williamson, Robin E
AU  - Williamson RE
AD  - Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
FAU - Darrow, Keith N
AU  - Darrow KN
FAU - Michaud, Sebastien
AU  - Michaud S
FAU - Jacobs, Julie S
AU  - Jacobs JS
FAU - Jones, Marilyn C
AU  - Jones MC
FAU - Eberl, Daniel F
AU  - Eberl DF
FAU - Maas, Richard L
AU  - Maas RL
FAU - Liberman, M Charles
AU  - Liberman MC
FAU - Morton, Cynthia C
AU  - Morton CC
LA  - eng
GR  - R01 DC0188/DC/NIDCD NIH HHS/United States
GR  - R01 DC004848-07/DC/NIDCD NIH HHS/United States
GR  - R01 DC000188-26/DC/NIDCD NIH HHS/United States
GR  - R01 DC000188/DC/NIDCD NIH HHS/United States
GR  - R01 DC03402/DC/NIDCD NIH HHS/United States
GR  - R01 DC04848/DC/NIDCD NIH HHS/United States
GR  - R01 DC004848-05/DC/NIDCD NIH HHS/United States
GR  - R01 DC004848-06/DC/NIDCD NIH HHS/United States
GR  - P01 GM061354/GM/NIGMS NIH HHS/United States
GR  - R01 DC004848/DC/NIDCD NIH HHS/United States
GR  - P30 DC005209/DC/NIDCD NIH HHS/United States
GR  - R01 DC000188-27/DC/NIDCD NIH HHS/United States
GR  - P30 DC5209/DC/NIDCD NIH HHS/United States
GR  - F31 DC005712/DC/NIDCD NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
RN  - EC 2.4.2.1 (Purine-Nucleoside Phosphorylase)
RN  - EC 2.4.2.28 (5'-methylthioadenosine phosphorylase)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Child, Preschool
MH  - Chromosomes, Human, Pair 9/genetics
MH  - *Disease Models, Animal
MH  - Drosophila melanogaster
MH  - Embryo, Nonmammalian/enzymology/metabolism
MH  - Female
MH  - Gene Expression Regulation, Enzymologic
MH  - Genes, Lethal
MH  - Hearing Loss/enzymology/*genetics/pathology
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Purine-Nucleoside Phosphorylase/*genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Translocation, Genetic
EDAT- 2007/05/31 09:00
MHDA- 2007/08/28 09:00
CRDT- 2007/05/31 09:00
PHST- 2007/05/31 09:00 [pubmed]
PHST- 2007/08/28 09:00 [medline]
PHST- 2007/05/31 09:00 [entrez]
AID - 10.1002/ajmg.a.31724 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2007 Jul 15;143A(14):1630-9. doi: 10.1002/ajmg.a.31724.