#153870
Table of Contents
Alternative titles; symbols
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-91 (RP91) is caused by heterozygous mutation in the IMPG1 gene (602870) on chromosome 6q14.
Heterozygous mutation in IMPG1 can also cause vitelliform macular dystrophy (VMD4; 616151).
Retinitis pigmentosa-91 (R91) is characterized by night blindness and constriction of visual fields, with bone-spicule pigmentation, attenuation of retinal vessels, and optic disc pallor on funduscopy. Patients may also experience early macular involvement, with photophobia and reduced visual acuity, and some show a bull's eye pattern of macular atrophy (Olivier et al., 2021).
In a grandmother and her daughter, granddaughter, and grandson, Deutman (1974) described a benign concentric annular macular dystrophy (BCAMD). The affected persons showed a depigmented ring around an intact central area, not unlike the eyes in chloroquin retinopathy and cone dystrophy. All 4 had almost normal acuity. Deutman (1974) found no definite report of the same disorder, but raised the question that the kindred reported by Martyn and Walker (1971) might have had the same condition. In a 15-year follow-up of the Dutch family reported by Deutman (1974), van Lith-Verhoeven et al. (2004) found a more pronounced involvement of the peripheral retina together with increased photoreceptor cell dysfunction, as found in RP.
Gonzalez-Gomez et al. (2019) reported a 44-year-old woman with maculopathy and a de novo splicing mutation in the IMPG1 gene. She presented at age 41 years with reduced visual acuity and showed annular (bull's eye) maculopathy with an intact central macula on funduscopy. Electroretinography showed nonspecific rod and cone dysfunction, and field testing revealed bilateral central scotoma. Over 3 years of follow-up, the patient experienced further reduction in visual acuity, particularly central vision, and dyschromatopsia; examination showed progression of atrophic areas. The authors noted phenotypic similarities to the Dutch family reported by Deutman (1974) and restudied by van Lith-Verhoeven et al. (2004).
Olivier et al. (2021) reexamined 10 affected members of the Dutch family (family L) that was originally reported by Deutman (1974) and diagnosed with benign concentric annular macular dystrophy. In the first 4 decades of life, fundus findings ranged from macular pigment alterations to a bull's eye maculopathy, sometimes accompanied by sparse bone spicule pigmentation, pallor of the optic disc, and attenuation of the retinal arterioles. When available, spectral-domain optic coherence tomography and fundus autofluorescence imaging revealed the loss of the outer retinal layers with sparing of the foveal photoreceptors. Two patients, aged 83 and 84 years, had visual function reduced to light perception. Another 2 family members were diagnosed with retinitis pigmentosa during screening, 9 and 3 years before the disease became symptomatic. Olivier et al. (2021) revised the diagnosis in this family from BCAMD to retinitis pigmentosa with early macular involvement.
Olivier et al. (2021) also reported 4 Spanish families (C, D, I, and K) and 2 French families (A and E) with RP and mutations in the IMPG1 gene. Fundus photographs showed typical changes of RP, including bone-spicule pigmentation in the periphery, retinal vessel attenuation, and pale optic discs.
The transmission pattern of retinitis pigmentosa in all but 2 of the families reported by Olivier et al. (2021) was consistent with autosomal dominant inheritance. Two families were reported to have autosomal recessive transmission of RP, but segregation was not shown and phenotypes of heterozygous carriers were not described.
By linkage analysis in a Dutch family with RP, originally reported by Deutman (1974) and diagnosed with BCAMD, van Lith-Verhoeven et al. (2004) established complete segregation of the phenotype (maximum multipoint lod score, 3.8) with DNA markers at chromosome 6p12.3-q16. Recombination events defined a critical interval spanning 30.7 cM at the long arm of chromosome 6 between markers D6S269 and D6S300.
In affected members of a 4-generation Dutch family with RP mapping to chromosome 6p12.3-q16, originally reported by Deutman (1974) and diagnosed with BCAMD, van Lith-Verhoeven et al. (2004) screened 5 candidate genes and identified heterozygosity for a missense mutation in the IMPG1 gene (L579P; 602870.0006). The mutation segregated with disease in the family and was not found in 190 control individuals. The authors noted that the mutation was not predicted to have a major effect on the protein, and stated that study of additional patients was necessary to establish the causality of the mutation.
Gonzalez-Gomez et al. (2019) reported a 44-year-old woman with annular (bull's eye) maculopathy and a de novo splicing mutation in the IMPG1 gene. She experienced progression of her disease, and the authors noted similarities to the phenotype of the Dutch family reported by Deutman (1974) and restudied by van Lith-Verhoeven et al. (2004).
By gene-panel testing and exome sequencing in 596 families with RP and vitelliform macular dystrophy (see VMD4, 616151), Olivier et al. (2021) identified IMPG1 mutations in 11 families, including 6 with RP (families A, C, D, E, I, and K), 2 with VMD (families B and G), and 1 (family F) in which both RP and VMD were diagnosed (see, e.g., 602870.0007-602870.0009). The mutations were heterozygous in 9 of the families; affected individuals in 2 Spanish families (D and K) were homozygous for IMPG1 variants, but segregation was not shown and the phenotypes of heterozygous carriers were not reported.
Coppeto and Ayazi (1982) observed wide variability in the affected members of 3 generations of a family: only dyschromatopsia in 6, dyschromatopsia and foveal hyperpigmentation in 1, and dyschromatopsia, foveal hyperpigmentation, and perifoveal circular pigment epithelial atrophy in 4. Normal findings on electrophysiologic testing suggested that this is a focal (macular) disorder rather than a generalized fundus disorder. No male-to-male transmission was observed.
Coppeto, J., Ayazi, S. Annular macular dystrophy. Am. J. Ophthal. 93: 279-284, 1982. [PubMed: 7072789, related citations] [Full Text]
Deutman, A. F. Benign concentric annular macular dystrophy. Am. J. Ophthal. 78: 384-396, 1974. [PubMed: 4412179, related citations] [Full Text]
Gonzalez-Gomez, A., Romero-Trevejo, J. L., Garcia-Ben, A., Garcia-Campos, J. M. Bull's eye maculopathy caused by a novel IMPG-1 mutation. Ophthalmic Genet. 40: 71-73, 2019. [PubMed: 30589393, related citations] [Full Text]
Martyn, L. J., Walker, B. A. A kindred showing a disorder of the retinal pigmentary epithelium and choliocapillaris, with characteristic macular changes and autosomal dominant transmission. Birth Defects Orig. Art. Ser. VII(3): 189-192, 1971.
Olivier, G., Corton, M., Intartaglia, D., Verbakel, S. K., Sergouniotis, P. I., Le Meur, G., Dhaenens, C.-M., Naacke, H., Avila-Fernandez, A., Hoyng, C. B., Klevering, J., Bocquet, B., and 12 others. Pathogenic variants in IMPG1 cause autosomal dominant and autosomal recessive retinitis pigmentosa. J. Med. Genet. 58: 570-578, 2021. [PubMed: 32817297, related citations] [Full Text]
van Lith-Verhoeven, J. J. C., Hoyng, C. B., van den Helm, B., Deutman, A. F., Brink, H. M. A., Kemperman, M. H., de Jong, W. H. M., Kremer, H., Cremers, F. P. M. The benign concentric annular macular dystrophy locus maps to 6p12.3-q16. Invest. Ophthal. Vis. Sci. 45: 30-35, 2004. [PubMed: 14691150, related citations] [Full Text]
Alternative titles; symbols
ORPHA: 251287;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 6q14.1 | Retinitis pigmentosa 91 | 153870 | Autosomal dominant | 3 | IMPG1 | 602870 |
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-91 (RP91) is caused by heterozygous mutation in the IMPG1 gene (602870) on chromosome 6q14.
Heterozygous mutation in IMPG1 can also cause vitelliform macular dystrophy (VMD4; 616151).
Retinitis pigmentosa-91 (R91) is characterized by night blindness and constriction of visual fields, with bone-spicule pigmentation, attenuation of retinal vessels, and optic disc pallor on funduscopy. Patients may also experience early macular involvement, with photophobia and reduced visual acuity, and some show a bull's eye pattern of macular atrophy (Olivier et al., 2021).
In a grandmother and her daughter, granddaughter, and grandson, Deutman (1974) described a benign concentric annular macular dystrophy (BCAMD). The affected persons showed a depigmented ring around an intact central area, not unlike the eyes in chloroquin retinopathy and cone dystrophy. All 4 had almost normal acuity. Deutman (1974) found no definite report of the same disorder, but raised the question that the kindred reported by Martyn and Walker (1971) might have had the same condition. In a 15-year follow-up of the Dutch family reported by Deutman (1974), van Lith-Verhoeven et al. (2004) found a more pronounced involvement of the peripheral retina together with increased photoreceptor cell dysfunction, as found in RP.
Gonzalez-Gomez et al. (2019) reported a 44-year-old woman with maculopathy and a de novo splicing mutation in the IMPG1 gene. She presented at age 41 years with reduced visual acuity and showed annular (bull's eye) maculopathy with an intact central macula on funduscopy. Electroretinography showed nonspecific rod and cone dysfunction, and field testing revealed bilateral central scotoma. Over 3 years of follow-up, the patient experienced further reduction in visual acuity, particularly central vision, and dyschromatopsia; examination showed progression of atrophic areas. The authors noted phenotypic similarities to the Dutch family reported by Deutman (1974) and restudied by van Lith-Verhoeven et al. (2004).
Olivier et al. (2021) reexamined 10 affected members of the Dutch family (family L) that was originally reported by Deutman (1974) and diagnosed with benign concentric annular macular dystrophy. In the first 4 decades of life, fundus findings ranged from macular pigment alterations to a bull's eye maculopathy, sometimes accompanied by sparse bone spicule pigmentation, pallor of the optic disc, and attenuation of the retinal arterioles. When available, spectral-domain optic coherence tomography and fundus autofluorescence imaging revealed the loss of the outer retinal layers with sparing of the foveal photoreceptors. Two patients, aged 83 and 84 years, had visual function reduced to light perception. Another 2 family members were diagnosed with retinitis pigmentosa during screening, 9 and 3 years before the disease became symptomatic. Olivier et al. (2021) revised the diagnosis in this family from BCAMD to retinitis pigmentosa with early macular involvement.
Olivier et al. (2021) also reported 4 Spanish families (C, D, I, and K) and 2 French families (A and E) with RP and mutations in the IMPG1 gene. Fundus photographs showed typical changes of RP, including bone-spicule pigmentation in the periphery, retinal vessel attenuation, and pale optic discs.
The transmission pattern of retinitis pigmentosa in all but 2 of the families reported by Olivier et al. (2021) was consistent with autosomal dominant inheritance. Two families were reported to have autosomal recessive transmission of RP, but segregation was not shown and phenotypes of heterozygous carriers were not described.
By linkage analysis in a Dutch family with RP, originally reported by Deutman (1974) and diagnosed with BCAMD, van Lith-Verhoeven et al. (2004) established complete segregation of the phenotype (maximum multipoint lod score, 3.8) with DNA markers at chromosome 6p12.3-q16. Recombination events defined a critical interval spanning 30.7 cM at the long arm of chromosome 6 between markers D6S269 and D6S300.
In affected members of a 4-generation Dutch family with RP mapping to chromosome 6p12.3-q16, originally reported by Deutman (1974) and diagnosed with BCAMD, van Lith-Verhoeven et al. (2004) screened 5 candidate genes and identified heterozygosity for a missense mutation in the IMPG1 gene (L579P; 602870.0006). The mutation segregated with disease in the family and was not found in 190 control individuals. The authors noted that the mutation was not predicted to have a major effect on the protein, and stated that study of additional patients was necessary to establish the causality of the mutation.
Gonzalez-Gomez et al. (2019) reported a 44-year-old woman with annular (bull's eye) maculopathy and a de novo splicing mutation in the IMPG1 gene. She experienced progression of her disease, and the authors noted similarities to the phenotype of the Dutch family reported by Deutman (1974) and restudied by van Lith-Verhoeven et al. (2004).
By gene-panel testing and exome sequencing in 596 families with RP and vitelliform macular dystrophy (see VMD4, 616151), Olivier et al. (2021) identified IMPG1 mutations in 11 families, including 6 with RP (families A, C, D, E, I, and K), 2 with VMD (families B and G), and 1 (family F) in which both RP and VMD were diagnosed (see, e.g., 602870.0007-602870.0009). The mutations were heterozygous in 9 of the families; affected individuals in 2 Spanish families (D and K) were homozygous for IMPG1 variants, but segregation was not shown and the phenotypes of heterozygous carriers were not reported.
Coppeto and Ayazi (1982) observed wide variability in the affected members of 3 generations of a family: only dyschromatopsia in 6, dyschromatopsia and foveal hyperpigmentation in 1, and dyschromatopsia, foveal hyperpigmentation, and perifoveal circular pigment epithelial atrophy in 4. Normal findings on electrophysiologic testing suggested that this is a focal (macular) disorder rather than a generalized fundus disorder. No male-to-male transmission was observed.
Coppeto, J., Ayazi, S. Annular macular dystrophy. Am. J. Ophthal. 93: 279-284, 1982. [PubMed: 7072789] [Full Text: https://doi.org/10.1016/0002-9394(82)90525-6]
Deutman, A. F. Benign concentric annular macular dystrophy. Am. J. Ophthal. 78: 384-396, 1974. [PubMed: 4412179] [Full Text: https://doi.org/10.1016/0002-9394(74)90225-6]
Gonzalez-Gomez, A., Romero-Trevejo, J. L., Garcia-Ben, A., Garcia-Campos, J. M. Bull's eye maculopathy caused by a novel IMPG-1 mutation. Ophthalmic Genet. 40: 71-73, 2019. [PubMed: 30589393] [Full Text: https://doi.org/10.1080/13816810.2018.1561903]
Martyn, L. J., Walker, B. A. A kindred showing a disorder of the retinal pigmentary epithelium and choliocapillaris, with characteristic macular changes and autosomal dominant transmission. Birth Defects Orig. Art. Ser. VII(3): 189-192, 1971.
Olivier, G., Corton, M., Intartaglia, D., Verbakel, S. K., Sergouniotis, P. I., Le Meur, G., Dhaenens, C.-M., Naacke, H., Avila-Fernandez, A., Hoyng, C. B., Klevering, J., Bocquet, B., and 12 others. Pathogenic variants in IMPG1 cause autosomal dominant and autosomal recessive retinitis pigmentosa. J. Med. Genet. 58: 570-578, 2021. [PubMed: 32817297] [Full Text: https://doi.org/10.1136/jmedgenet-2020-107150]
van Lith-Verhoeven, J. J. C., Hoyng, C. B., van den Helm, B., Deutman, A. F., Brink, H. M. A., Kemperman, M. H., de Jong, W. H. M., Kremer, H., Cremers, F. P. M. The benign concentric annular macular dystrophy locus maps to 6p12.3-q16. Invest. Ophthal. Vis. Sci. 45: 30-35, 2004. [PubMed: 14691150] [Full Text: https://doi.org/10.1167/iovs.03-0392]
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