Fpm Cremers

The ABCA4 2588G>C Stargardt mutation: single origin and increasing frequency from South-West to North-East Europe.

Inherited retinal dystrophies represent the most important cause of vision impairment in adolescence, affecting approximately 1 out of 3000 individuals. Mutations of the photoreceptor-specific gene ABCA4 (ABCR) are a common cause of retinal dystrophy. A number of mutations have been repeatedly reported for this gene, notably the 2588G>C mutation which is frequent in both patients and controls. Here we ascertained the frequency of the 2588G>C mutation in a total of 2343 unrelated random control individuals from 11 European countries and 241 control individuals from the US, as well as in 614 patients with STGD both from Europe and the US. We found an overall carrier frequency of 1 out of 54 in Europe, compared with 1 out of 121 in the US, confirming that the 2588G>C ABCA4 mutation is one of the most frequent autosomal recessive mutations in the European population. Carrier frequencies show an increasing gradient in Europe from South-West to North-East. The lowest carrier frequency, 0 out of 199 (0%), was found in Portugal; the highest, 11 out of 197 (5.5%), was found in Sweden. Haplotype analysis in 16 families segregating the 2588G>C mutation showed four intragenic polymorphisms invariably present in all 16 disease chromosomes and sharing of the same allele for several markers flanking the ABCA4 locus in most of the disease chromosomes. These results indicate a single origin of the 2588G>C mutation which, to our best estimate, occurred between 2400 and 3000 years ago.

Homozygosity mapping identifies genetic defects in four consanguineous families with retinal dystrophy from Pakistan.

To the Editor : Retinitis pigmentosa (RP) is a progressive retinal degeneration, which primarily affects rod photoreceptor cells. Typical RP features include nyctalopia, bone spicule pigmentation, attenuation of retinal arterioles, and reduced electroretinogram (ERG) (1). Defects in 36 genes are known for autosomal recessive RP (arRP) (http://www.sph.uth.tmc.edu/retnet), which explain the disease in about 50% of the patients (2). Homozygosity mapping has been very successful in identifying genetic defects in the Pakistani population as >80% of families show consanguinity. Homozygosity mapping was utilized to identify genetic defects in four consanguineous Pakistani families. Patients were informed about the aims and objectives of the project before obtaining consent. Affected persons from families RP03, RP48, and RP55 had typical features of classical RP (Table 1). In family RP27, early-onset RP was observed along with macular degeneration, which is indistinguishable from Leber congenital amaurosis (LCA), as reported previously in some cases (Table 1) (3). Genomic DNA samples of selected persons were analyzed using whole genome single nucleotide polymorphism arrays (Fig. 1a). Family RP27 was genotyped using the Illumina 6K array, while families RP03, RP48, and RP55 were analyzed

Genetics and Diagnostics of Retinitis Pigmentosa

Purpose To utilize next generation sequencing (NGS) and identity‐by‐descent mapping to identify mutations in known and new genes in patients with autosomal recessive (ar) or isolated (i) retinitis pigmentosa (RP).