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Thaddeus P. Dryja, David E. Rucinski, Sherleen Huang Chen, Eliot L. Berson; Frequency of Mutations in the Gene Encoding the α Subunit of Rod cGMP-Phosphodiesterase in Autosomal Recessive Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 1999;40(8):1859-1865.
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purpose. To determine the mutation spectrum of the PDE6A gene encoding theα
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
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 β subunit of rod
cGMP-phosphodiesterase shows that the cGMP-binding and catalytic
domains are frequently affected.
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