current
RPE65:c.1102T>C (p.Tyr368His) AND Retinitis pigmentosa 20
current
classified by single submitter
Pathogenic
germline
human
not provided
curation
In 2 brothers with severe retinal dystrophy in childhood that progressed to near-total vision loss in adulthood (RP20; 613794), Felius et al. (2002) identified compound heterozygosity for a 1156T-C transition in the RPE65 gene, resulting in a tyr368-to-his (Y368H) substitution at a conserved residue, and a +5G-A transition in intron 1 (IVS1+5G-A; 180069.0010). Their asymptomatic mother, who carried the Y368H mutation, had normal visual acuity, light- and dark-adapted visual fields, and electroretinograms (ERGs). Their father, who carried the splice site mutation and also had no vision complaints, was found to have peripheral rod dysfunction and hundreds of tiny hard drusen covering his maculae bilaterally, extending into the rod-rich retina beyond the macular arcades.
11786058
In 13 patients with early-onset severe retinal dystrophy (LCA2; 204100) from 9 related Dutch families from a genetically isolated population living on a former island, Yzer et al. (2003) identified homozygosity for the Y368H mutation in the RPE65 gene. A patient from another related family was found to be compound heterozygous for Y368H and the IVS1+5G-A splice site mutation. Among 25 unaffected sibs tested, 17 were heterozygous for the Y368H mutation and 8 did not carry the mutation, and the Y368H mutation was found in 3 (3.1%) of 96 unrelated controls from the same isolated population. Yzer et al. (2003) stated that the Y368H mutation most likely represented a founder mutation inherited from a common ancestor of all 10 Dutch families who was born in the 18th century or earlier. The authors noted that in a study of the same genetically isolated Dutch population, Schappert-Kimmijser et al. (1959) ascertained 13 LCA patients in 8 families; Yzer et al. (2003) predicted that most if not all of those patients carried the Y368H founder mutation. Y368H was not detected in 86 LCA patients from a different white population or in 94 controls from the Netherlands, but analysis of 75 Dutch patients with autosomal recessive or isolated retinitis pigmentosa revealed the presence of the mutation in heterozygosity in 1 Dutch patient with RP and early-onset vision loss.
12960219
13616783
RPE65:c.1102T>C (p.Tyr368His)
NM_000329.2:c.1102T>C
NG_008472.1:g.16747T>C
NC_000001.10:g.68903896A>G
NP_000320.1:p.Tyr368His
missense
Y368H
TYR368HIS
1p31.2
retinal pigment epithelium-specific protein 65kDa
RPE65
Retinitis pigmentosa 20
RP 20
RP20
Retinitis pigmentosa (RP) is a group of inherited disorders in which abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium (RPE) of the retina lead to progressive visual loss. Affected individuals first experience defective dark adaptation or "night blindness," followed by constriction of peripheral visual fields and, eventually, loss of central vision late in the course of the disease.
Variable
1-5 / 10 000
20301590
current
pathogenic
germline
human
not provided
curation
In 2 brothers with severe retinal dystrophy in childhood that progressed to near-total vision loss in adulthood (RP20; 613794), Felius et al. (2002) identified compound heterozygosity for a 1156T-C transition in the RPE65 gene, resulting in a tyr368-to-his (Y368H) substitution at a conserved residue, and a +5G-A transition in intron 1 (IVS1+5G-A; 180069.0010). Their asymptomatic mother, who carried the Y368H mutation, had normal visual acuity, light- and dark-adapted visual fields, and electroretinograms (ERGs). Their father, who carried the splice site mutation and also had no vision complaints, was found to have peripheral rod dysfunction and hundreds of tiny hard drusen covering his maculae bilaterally, extending into the rod-rich retina beyond the macular arcades.
11786058
In 13 patients with early-onset severe retinal dystrophy (LCA2; 204100) from 9 related Dutch families from a genetically isolated population living on a former island, Yzer et al. (2003) identified homozygosity for the Y368H mutation in the RPE65 gene. A patient from another related family was found to be compound heterozygous for Y368H and the IVS1+5G-A splice site mutation. Among 25 unaffected sibs tested, 17 were heterozygous for the Y368H mutation and 8 did not carry the mutation, and the Y368H mutation was found in 3 (3.1%) of 96 unrelated controls from the same isolated population. Yzer et al. (2003) stated that the Y368H mutation most likely represented a founder mutation inherited from a common ancestor of all 10 Dutch families who was born in the 18th century or earlier. The authors noted that in a study of the same genetically isolated Dutch population, Schappert-Kimmijser et al. (1959) ascertained 13 LCA patients in 8 families; Yzer et al. (2003) predicted that most if not all of those patients carried the Y368H founder mutation. Y368H was not detected in 86 LCA patients from a different white population or in 94 controls from the Netherlands, but analysis of 75 Dutch patients with autosomal recessive or isolated retinitis pigmentosa revealed the presence of the mutation in heterozygosity in 1 Dutch patient with RP and early-onset vision loss.
12960219
13616783
RPE65, TYR368HIS
TYR368HIS
RPE65
RETINITIS PIGMENTOSA 20