PMID- 10393062
OWN - NLM
STAT- MEDLINE
DCOM- 19990708
LR  - 20220331
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 40
IP  - 8
DP  - 1999 Jul
TI  - Frequency of mutations in the gene encoding the alpha subunit of rod
      cGMP-phosphodiesterase in autosomal recessive retinitis pigmentosa.
PG  - 1859-65
AB  - PURPOSE: To determine the mutation spectrum of the PDE6A gene encoding the alpha 
      subunit of rod cyclic guanosine monophosphate (cGMP)phosphodiesterase and the
      proportion of patients with recessive retinitis pigmentosa (RP) due to mutations 
      in this gene. METHODS: The single-strand conformation polymorphism (SSCP)
      technique and a direct genomic sequencing technique were used to screen all 22
      exons of this gene for mutations in 164 unrelated patients with recessive or
      isolate RP. Variant DNA fragments revealed by SSCP analysis were subsequently
      sequenced. Selected alleles that altered the coding region or intron splice sites
      were evaluated further through segregation analysis in the families of the index 
      cases. RESULTS: Four new families were identified with five novel mutations in
      this gene that cosegregated with disease. Combining the data presented here with 
      those published earlier by the authors, eight different mutations in six families
      have been discovered to be pathogenic. Two of the mutations are nonsense, five
      are missense, and one affects a canonical splice-donor site. CONCLUSIONS: The
      PDE6A gene appears to account for roughly 3% to 4% of families with recessive RP 
      in North America. A compilation of the pathogenic mutations in PDE6A and those
      reported in the homologous gene PDE6B encoding the beta subunit of rod
      cGMP-phosphodiesterase shows that the cGMP-binding and catalytic domains are
      frequently affected.
FAU - Dryja, T P
AU  - Dryja TP
AD  - Ocular Molecular Genetics Institute, Harvard Medical School, Massachusetts Eye
      and Ear Infirmary, Boston 02114, USA.
FAU - Rucinski, D E
AU  - Rucinski DE
FAU - Chen, S H
AU  - Chen SH
FAU - Berson, E L
AU  - Berson EL
LA  - eng
GR  - EY00169/EY/NEI NIH HHS/United States
GR  - EY08683/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (DNA Primers)
RN  - 0 (Eye Proteins)
RN  - EC 3.1.4.35 (3',5'-Cyclic-GMP Phosphodiesterases)
RN  - EC 3.1.4.35 (Cyclic Nucleotide Phosphodiesterases, Type 6)
RN  - EC 3.1.4.35 (PDE6C protein, human)
SB  - IM
MH  - 3',5'-Cyclic-GMP Phosphodiesterases/*genetics
MH  - Cyclic Nucleotide Phosphodiesterases, Type 6
MH  - DNA Primers/chemistry
MH  - Exons/genetics
MH  - Eye Proteins/*genetics
MH  - Female
MH  - *Gene Frequency
MH  - *Genes, Recessive
MH  - Humans
MH  - Male
MH  - Pedigree
MH  - *Point Mutation
MH  - Polymorphism, Single-Stranded Conformational
MH  - Retinal Rod Photoreceptor Cells/*enzymology
MH  - Retinitis Pigmentosa/enzymology/*genetics
MH  - Sequence Analysis, DNA
EDAT- 1999/07/07 00:00
MHDA- 1999/07/07 00:01
CRDT- 1999/07/07 00:00
PHST- 1999/07/07 00:00 [pubmed]
PHST- 1999/07/07 00:01 [medline]
PHST- 1999/07/07 00:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 1999 Jul;40(8):1859-65.