Identification of GUCY2D gene mutations in CORD5 families and evidence of incomplete penetrance.
Cone rod dystrophy 5 (CORD5) is an autosomal dominant retinal disease that primarily affects cone function. The locus has previously been mapped to human chromosome 17p12-p13 between the markers D17S926/D17S849 and D17S945/D17S804. One of our "unaffected" recombinant individual from family 1175 was subsequently found to cross through this interval. Reexamination revealed that he was in fact mildly affected. This expanded the minimum candidate region. Direct sequencing of the GUCY2D and other candidate genes within this interval was carried out on 2 American families affected with CORD5. There was an R838C missense mutation within the GUCY2D gene in one and a R838H missense mutation in another families. The previously reported mutations for CORD6 are clustered at the same position within the gene. These results indicate that both CORD5 (MIM# 600977) and CORD6 (MIM# 601777) are actually the same disease. We conclude that significant variability in expression and incomplete penetrance exists even within one family.
Udar
Nitin
N
Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA.
Yelchits
Svetlana
S
Chalukya
Meenal
M
Yellore
Vivek
V
Nusinowitz
Steve
S
Silva-Garcia
Rosamaria
R
Vrabec
Tamara
T
Hussles Maumenee
Irene
I
Donoso
Larry
L
Small
Kent W
KW
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000235:genetics; D002417:Cattle; D002648:Child; D002675:Child, Preschool; D004285:Dogs; D020900:Echinacea / Q000235:genetics; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006162:Guanylate Cyclase / Q000235:genetics*; D006639:Histidine / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D015418:Optic Atrophies, Hereditary / Q000201:enzymology* / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D010940:Plant Proteins / Q000235:genetics; D051381:Rats; D011995:Recombination, Genetic / Q000235:genetics
D005819:Genetic Markers; D010940:Plant Proteins; D006639:Histidine; D001120:Arginine; D006162:Guanylate Cyclase