Macular Dystrophy, Vitelliform, 1

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

PRPH2, BEST1, IMPG1, IMPG2, TST, PRPH, CACD, TIMP3

Drugs

Adeno-associated virus serotype 8 containing the human RdCVF sequence and the human RdCVFL sequence, Combination of three adeno-associated viral vectors of serotype 8 containing the 5'-, the body- and the 3'- coding sequences of human CEP290 fused to inteins

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Description

Macular dystrophies are inherited retinal dystrophies in which various forms of deposits, pigmentary changes, and atrophic lesions are observed in the macula lutea, the cone-rich region of the central retina. Vitelliform macular dystrophies (VMDs) form a subset of macular dystrophies characterized by round yellow deposits, usually at the center of the macula and containing lipofuscin, a chemically heterogeneous pigment visualized by autofluorescence imaging of the fundus (summary by Manes et al., 2013). In contrast to typical VMD (see 153700), patients with atypical VMD may exhibit normal electrooculography, even when severe loss of vision is present, and fluorescein angiography is thus the most reliable test for identifying affected individuals (Hittner et al., 1984).

Genetic Heterogeneity of Vitelliform Macular Dystrophy

See also vitelliform macular dystrophy-2 (VMD2; 153700), caused by mutation in the BEST1 gene (607854) on chromosome 11q; VMD3 (608161), caused by mutation in the PRPH2 gene (179605) on chromosome 6p21; VMD4 (616151), caused by mutation in the IMPG1 gene (602870) on chromosome 6q14; and VMD5 (616152), caused by mutation in the IMPG2 gene (607056) on chromosome 3q12.

Clinical Features

Ferrell et al. (1983) reported a large family segregating autosomal dominant atypical vitelliform macular dystrophy. In this family, fluorescein angiography was more helpful than electrooculogram (EOG) in ascertaining affected persons. Early signs were minimal angiographic changes in the macula and peripapillary region, and small yellow lesions in the macula and periphery. Moderate accumulations of the yellow material in the central and peripheral retina, and advanced depigmented lesions of the central and peripheral retina and peripapillary region were also documented in family members. These findings were similar to those in typical vitelliform macular dystrophy (153700), which involves the retinal pigment epithelium (RPE) and invariably has an abnormal EOG.

Hittner et al. (1984) reported further on the 5-generation family studied by Ferrell et al. (1983). Forty-three of 101 at-risk members were affected (43%). Vision varied from 20/20 to 20/200. EOG studies were normal or reduced and did not correlate with visual acuity. Retinal findings consisted of macular or extramacular punctate yellow lesions or both in the RPE, which were hypofluorescent by angiography.

Mapping

This form of VMD was erroneously reported as being linked to the soluble GPT1 locus (138200), which had provisionally been mapped to chromosome 16p, by Ferrell et al. (1983). They found a maximum lod score of 4.34 at a recombination fraction of 0.05. However, the lods for PGP (172280), which is on 16p, and for haptoglobin (140100), which is on 16q, were negative and not significantly positive, respectively. With the mapping of GPT1 to 8q24, Sohocki et al. (1997) reexamined the localization of the VMD1 locus in the family reported by Ferrell et al. (1983). Using a newly developed PCR-RFLP assay for GPT typing, they corrected the GPT types of several individuals from the original study and found no linkage between VMD1 and GPT1. Sohocki et al. (1997) also excluded linkage of VMD1 with known autosomal dominant macular dystrophy loci.

Genotype/Phenotype Correlations

Meunier et al. (2014) reviewed 76 families with vitelliform macular dystrophy and found that 24 (53%) of 45 families with onset of disease before 40 years of age had a mutation in the BEST1 gene (607854), whereas 3 (9.7%) of 31 families with onset after 40 years of age had a mutation in the PRPH2 gene (179605). For the remaining 49 families without a mutation in BEST1 or PRPH2, 3 (6%) had a mutation in the IMPG1 gene and 1 (2%) in the IMPG2 gene (607056). Meunier et al. (2014) stated that the IMPG1 and IMPG2 vitelliform macular dystrophies are characterized by late-onset moderate visual impairment, frequent association with drusen-like lesions, preservation of RPE reflectivity, lack of sub-RPE deposits on spectral-domain optical coherence tomography (SD-OCT), and normal or borderline results on EOG. The authors noted that although patients with a BEST1 mutation were most frequently symptomatic before the age of 40 years, there was overlap with PRPH2 patients in terms of age of onset; in addition, the presence of small satellite drusen-like lesions in the foveal area appeared to implicate the IMPG1 or IMPG2 genes.