Codons 837 and 838 in the Retinal Guanylate Cyclase Gene on Chromosome 17p: Hot Spots for Mutations in Autosomal Dominant Cone-Rod Dystrophy?

Clustering and frequency of mutations in the retinal guanylate cyclase (GUCY2D) gene in patients with dominant cone-rod dystrophies

“…This indicates that either the R838C mutations have arisen separately from each other or that a single mutation occurred in a much more distant ancestor than the common mutation for Sorsby's fundus dystrophy, with a consequent wider distribution in the population. Furthermore and again irrespective of the presence or absence of a common ancestor for our R838C families, the occurrence of the R838C mutation in a presumably unrelated Norwegian family,7 the R838H mutations in one of our British families and in a Swiss family,6 and the multiple mutations in codon 838 and adjacent codons in the original CORD6 family,4 as well as in a French family,5 all identify this codon as particularly mutation prone.…”

“…In all seven families, the mutations are either in the same or in adjacent codons in a highly conserved region of the protein. In our four families and in the Swiss and Norwegian families, mutations were found in either codon 837 or 838,4 6 7 whereas codons 837-839 each encode for an amino acid substitution in the French family 5…”

Clustering and frequency of mutations in the retinal guanylate cyclase (GUCY2D) gene in patients with dominant cone-rod dystrophies

“…This indicates that either the R838C mutations have arisen separately from each other or that a single mutation occurred in a much more distant ancestor than the common mutation for Sorsby's fundus dystrophy, with a consequent wider distribution in the population. Furthermore and again irrespective of the presence or absence of a common ancestor for our R838C families, the occurrence of the R838C mutation in a presumably unrelated Norwegian family,7 the R838H mutations in one of our British families and in a Swiss family,6 and the multiple mutations in codon 838 and adjacent codons in the original CORD6 family,4 as well as in a French family,5 all identify this codon as particularly mutation prone.…”

“…In all seven families, the mutations are either in the same or in adjacent codons in a highly conserved region of the protein. In our four families and in the Swiss and Norwegian families, mutations were found in either codon 837 or 838,4 6 7 whereas codons 837-839 each encode for an amino acid substitution in the French family 5…”

Whole Exome Sequencing Reveals GUCY2D as a Major Gene Associated With Cone and Cone-Rod Dystrophy in Israel

“…The three dominant families harbored heterozygous GUCY2D missense mutations that have been reported previously (Table 1): c.2512C>T (p.R838C) 17 in families MOL0490 and MOL1103, and c.2513G>A (p.R838H) 18 in family MOL0859. This result suggested that GUCY2D mutations, although not previously described in Israeli patients, might be a significant cause of AD cone-dominated disease.…”

Use of Spectral Domain-Optical Coherence Tomography to Visualize Photoreceptor Abnormalities in Cone-Rod Dystrophy 6

“…Codon 838 is part of a 3 codon sequence within the putative dimerization domain of the protein. The heterozygous Arg838His mutation has been previously reported for dominantly inherited CORD6 6. Interestingly, homozygous mutations in GUCY2D can lead to recessively inherited Leber’s congenital amaurosis 7…”

Clustering and frequency of mutations in the retinal guanylate cyclase (GUCY2D) gene in patients with dominant cone-rod dystrophies

“…This indicates that either the R838C mutations have arisen separately from each other or that a single mutation occurred in a much more distant ancestor than the common mutation for Sorsby's fundus dystrophy, with a consequent wider distribution in the population. Furthermore and again irrespective of the presence or absence of a common ancestor for our R838C families, the occurrence of the R838C mutation in a presumably unrelated Norwegian family,7 the R838H mutations in one of our British families and in a Swiss family,6 and the multiple mutations in codon 838 and adjacent codons in the original CORD6 family,4 as well as in a French family,5 all identify this codon as particularly mutation prone.…”

“…In all seven families, the mutations are either in the same or in adjacent codons in a highly conserved region of the protein. In our four families and in the Swiss and Norwegian families, mutations were found in either codon 837 or 838,4 6 7 whereas codons 837-839 each encode for an amino acid substitution in the French family 5…”

Whole Exome Sequencing Reveals GUCY2D as a Major Gene Associated With Cone and Cone-Rod Dystrophy in Israel

“…The three dominant families harbored heterozygous GUCY2D missense mutations that have been reported previously (Table 1): c.2512C>T (p.R838C) 17 in families MOL0490 and MOL1103, and c.2513G>A (p.R838H) 18 in family MOL0859. This result suggested that GUCY2D mutations, although not previously described in Israeli patients, might be a significant cause of AD cone-dominated disease.…”

Use of Spectral Domain-Optical Coherence Tomography to Visualize Photoreceptor Abnormalities in Cone-Rod Dystrophy 6

“…Codon 838 is part of a 3 codon sequence within the putative dimerization domain of the protein. The heterozygous Arg838His mutation has been previously reported for dominantly inherited CORD6 6. Interestingly, homozygous mutations in GUCY2D can lead to recessively inherited Leber’s congenital amaurosis 7…”

Clustering and frequency of mutations in the retinal guanylate cyclase (GUCY2D) gene in patients with dominant cone-rod dystrophies

“…This indicates that either the R838C mutations have arisen separately from each other or that a single mutation occurred in a much more distant ancestor than the common mutation for Sorsby's fundus dystrophy, with a consequent wider distribution in the population. Furthermore and again irrespective of the presence or absence of a common ancestor for our R838C families, the occurrence of the R838C mutation in a presumably unrelated Norwegian family,7 the R838H mutations in one of our British families and in a Swiss family,6 and the multiple mutations in codon 838 and adjacent codons in the original CORD6 family,4 as well as in a French family,5 all identify this codon as particularly mutation prone.…”

“…In all seven families, the mutations are either in the same or in adjacent codons in a highly conserved region of the protein. In our four families and in the Swiss and Norwegian families, mutations were found in either codon 837 or 838,4 6 7 whereas codons 837-839 each encode for an amino acid substitution in the French family 5…”

Whole Exome Sequencing Reveals GUCY2D as a Major Gene Associated With Cone and Cone-Rod Dystrophy in Israel

“…The three dominant families harbored heterozygous GUCY2D missense mutations that have been reported previously (Table 1): c.2512C>T (p.R838C) 17 in families MOL0490 and MOL1103, and c.2513G>A (p.R838H) 18 in family MOL0859. This result suggested that GUCY2D mutations, although not previously described in Israeli patients, might be a significant cause of AD cone-dominated disease.…”

Use of Spectral Domain-Optical Coherence Tomography to Visualize Photoreceptor Abnormalities in Cone-Rod Dystrophy 6

“…Codon 838 is part of a 3 codon sequence within the putative dimerization domain of the protein. The heterozygous Arg838His mutation has been previously reported for dominantly inherited CORD6 6. Interestingly, homozygous mutations in GUCY2D can lead to recessively inherited Leber’s congenital amaurosis 7…”