Fundus albipunctatus and retinitis punctata albescens in a pedigree with an R150Q mutation in RLBP1

Abstract

Fundus albipunctatus (FA; OMIM 136880) is a rare form of apparently stationary night blindness characterized by the presence of myriad symmetrical round white dots in the fundus with a greater concentration in the midperiphery. A distantly similar but distinct clinical entity, retinitis punctata albescens (RPA), is also characterized by aggregation of irregular white flecks but is progressive and evolves to generalized atrophy of the retina. We studied 4 consanguineous kindreds diagnosed with FA from Saudi Arabia. Given the substantial phenotypic variation and overlap between different flecked retinal dystrophies, we evaluated all known genes associated with such conditions by both genetic analysis and direct sequencing. In one kindred, KKESH-099, we identified a homozygous R150Q alteration in RLBP1, the gene encoding the cellular retinaldehyde binding protein, associated previously with both recessive retinitis pigmentosa (arRP) and RPA. Examination of several patients aged 3-20 years over a 9-year period presented no evidence for either RP or RPA. In contrast, clinical examination of individuals with the same mutation in their fourth and fifth decade revealed signs consistent with RPA. The data suggest that the R150Q mutation in RLBP1 may result in RPA with slow progression. More importantly, younger individuals diagnosed with the milder disorder FA thought to be stationary may evolve to a more devastating and progressive phenotype.

Retinitis Pigmentosa in Northern Sweden - From Gene to Treatment

“…9). RPA or subtle white lesions of the fundus have previously been described in several autosomal recessive RP cases with RLBP1 mutations, and also in other progressive degenerative diseases, for example, the rhodopsin-related RP (Demirci et al, 2004;Eichers et al, 2002;Fishman et al, 2004;Katsanis et al, 2001;Nakamura et al, 2005;Souied et al, 1996). The localization of RPA lesions and their appearance may resemble more commonly known retinal lesions like drusen in age-related macular degeneration.…”

“…First homozygous RLBP1 mutation was found in a consanguineous family of Indian origin and in one of consanguineous kindred from Saudi Arabia, both diagnosed with retinitis punctata albescens (Maw et al, 1997;Katsanis et al, 2001). Three additional mutations in the RLBP1 gene were identified in the patients of European ancestry with recessively inherited RPA (Morimura et al, 1999), and in patients of Newfoundland origin with a severe rod cone dystrophy two splice junction mutations were detected (Eichers et al, 2002).…”

A novel compound heterozygous mutation in the cellular retinaldehyde-binding protein gene (RLBP1) in a patient with retinitis punctata albescens

“…However, the current published data are insufficient to infer a meaningful genotype-phenotype correlation. The phenotypic variability reported for the same mutations 1,4,5 suggests that other genetic or environmental factors may modify the clinical state. Identification of these novel mutations contribute to the structure-function studies that may guide future therapeutic efforts in these patients.…”

“…A recent study revealed that the same RLBP1 mutation may cause FA in the first two to three decades of life and RPA in the fourth to fifth decades, suggesting that some young patients with seemingly stationary night blindness may eventually develop a progressive-atrophic phenotype. 5 The distinctions among FA, RPA, BD, NFRCD, and RP are poorly defined and depend on the age of onset, age at diagnosis, progression rate, and severity.…”

VII-2 : ELECTROPHYSIOLOGIE PEDIATRIQUE : EXEMPLES Première partie

“…La rétinopathie ponctuée albescente est autosomique récessive toujours progressive mais cependant d'évolution lente vers une atrophie rétinienne, avec atteinte majeure du système scotopique (Katsanis et al, 2001). …”