Localization of the gene for progressive bifocal chorioretinal atrophy (PBCRA) to chromosome 6q

Abstract

Progressive bifocal chorioretinal atrophy (PBCRA) is a rare, autosomal dominant congenital chorioretinal dystrophy. We have performed genetic linkage analysis on a five-generation British pedigree. Two-point linkage analysis showed significant linkage with nine microsatellite marker loci mapping to chromosome 6q. Multipoint analysis gave a maximum lod score of 11.8 (theta = 0.05) between D6S249 and D6S283. This region overlaps with that to which the gene for North Carolina macular dystrophy (MCDR1) has been assigned. However, given the range of differences in phenotype between these two retinal disorders, it is likely that different mutation mechanisms are responsible for each disease.

Genomic organization and chromosomal localization of the interphotoreceptor matrix proteoglycan-1 (IMPG1) gene: a candidate for 6q-linked retinopathies

“…The selective expression in retinal tissue and the chromosomal mapping of IMPG1 to 6q13-q15 have identified this gene as an attractive candidate for several human macular dystrophies that have previously been localized to 6q11 → q16.2 by genetic linkage analysis, viz., autosomal dominant Stargardtlike macular dystrophy (STGD3) (Stone et al, 1994), North Carolina macular dystrophy (MCDR1) (Small et al, 1992), and progressive bifocal chorioretinal atrophy (PBCRA) (Kelsell et al, 1995) (Fig. 6).…”

Childhood macular dystrophies

“…Recently Yang et al [15] have refined the locus to a 3-cm region between markers D6S1716 and D6S1671 and screened the coding regions of all 11 genes in the refined region in six families; no mutations were identified suggesting that the disorder is due to a mutation in a regulatory region or a copy number variant. Another rare autosomal dominant developmental macular disorder -progressive bifocal chorioretinal atrophy (PBCRA) [16] -maps to an overlapping locus on chromosome 6q and again the causative mutation has yet to be identified [17]. It is unclear if PBCRA and NCMD are allelic or whether there are two closely related developmental genes on chromosome 6q.…”

Genetic linkage analysis of a novel syndrome comprising North Carolina-like macular dystrophy and progressive sensorineural hearing loss

“…13 The gene for NCMD has been shown to reside within a 3.1 cM interval termed the MCDR1 locus on 6q14-q16.2 [14][15] ). Interestingly, NCMD co-localises with bifocal chorioretinal atrophy with which it shares some clinical similarities 2 and lies adjacent to the loci for Stargardt-like dominant progressive macular dystrophy, 16 autosomal dominant macular atrophy, 17 cone-rod dystrophy 7, 18 autosomal dominant drusen and macular degeneration, 19 and the recessive retinitis pigmentosa 25 locus. 20 NCMD is a fully penetrant dominant disease with variable expressivity and onset in infancy.…”