A Nonsense Mutation in FAM161A Is a Recurrent Founder Allele in Dutch and Belgian Individuals With Autosomal Recessive Retinitis Pigmentosa.

Purpose: To identify mutations in FAM161A underlying autosomal recessive retinitis pigmentosa (arRP) in the Dutch and Belgian populations and to investigate whether common FAM161A-associated phenotypic features could be identified.

Methods: Homozygosity mapping, amplification-refractory mutation system (ARMS) analysis, and Sanger sequencing were performed to identify mutations in FAM161A. Microsatellite and SNP markers were genotyped for haplotype analysis.

Identification of mutations causing inherited retinal degenerations in the israeli and palestinian populations using homozygosity mapping.

Purpose: The Israeli and Palestinian populations are known to have a relatively high level of consanguineous marriages, leading to a relatively high frequency of autosomal recessive (AR) diseases. Our purpose was to use the homozygosity mapping approach, aiming to prioritize the set of genes and identify the molecular genetic causes underlying AR retinal degenerations in the Israeli and Palestinian populations.

Methods: Clinical analysis included family history, ocular examination, full-field electroretinography (ERG), and funduscopy.

Mutations in CRB1 are a relatively common cause of autosomal recessive early-onset retinal degeneration in the Israeli and Palestinian populations.

Purpose: We evaluated the role of Crumbs homolog 1 (CRB1) in autosomal recessive (AR) retinal diseases in the Israeli and Palestinian populations using homozygosity mapping.

Methods: Clinical analysis included family history, ocular examination, full-field electroretinography (ERG), and funduscopy. Molecular analysis included homozygosity mapping using whole genome single nucleotide polymorphism (SNP) arrays and mutation analysis of CRB1.

FAM161A, associated with retinitis pigmentosa, is a component of the cilia-basal body complex and interacts with proteins involved in ciliopathies.

Retinitis pigmentosa (RP) is a retinal degenerative disease characterized by the progressive loss of photoreceptors. We have previously demonstrated that RP can be caused by recessive mutations in the human FAM161A gene, encoding a protein with unknown function that contains a conserved region shared only with a distant paralog, FAM161B. In this study, we show that FAM161A localizes at the base of the photoreceptor connecting cilium in human, mouse and rat.

Enhanced S-cone function with preserved rod function: a new clinical phenotype.

Purpose: To describe the clinical findings and genetic analysis in two brothers having a novel retinal disease characterized by an enhanced S-cone phenotype with normal rod function.

Methods: Both patients underwent complete ophthalmologic examinations, including fundus photography, electroretinography (ERG), fluorescein angiography and optical coherence tomography (OCT). Mutation analysis of the following candidate genes was performed: nuclear receptor subfamily 2 group E member 3 (NR2E3), neural retina leucine zipper (NRL), nuclear receptor subfamily 1 group D member 1 (NR1D1), and thyroid hormone receptor beta (THRB).

A missense mutation in DHDDS, encoding dehydrodolichyl diphosphate synthase, is associated with autosomal-recessive retinitis pigmentosa in Ashkenazi Jews.

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations caused by mutations in at least 50 genes. Using homozygosity mapping in Ashkenazi Jewish (AJ) patients with autosomal-recessive RP (arRP), we identified a shared 1.7 Mb homozygous region on chromosome 1p36.

Homozygosity mapping reveals null mutations in FAM161A as a cause of autosomal-recessive retinitis pigmentosa.

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations caused by mutations in at least 45 genes. Using homozygosity mapping, we identified a ∼4 Mb homozygous region on chromosome 2p15 in patients with autosomal-recessive RP (arRP). This region partially overlaps with RP28, a previously identified arRP locus.

Mutations in IMPG2, encoding interphotoreceptor matrix proteoglycan 2, cause autosomal-recessive retinitis pigmentosa.

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases caused by progressive degeneration of the photoreceptor cells. Using autozygosity mapping, we identified two families, each with three affected siblings sharing large overlapping homozygous regions that harbored the IMPG2 gene on chromosome 3. Sequence analysis of IMPG2 in the two index cases revealed homozygous mutations cosegregating with the disease in the respective families: three affected siblings of Iraqi Jewish ancestry displayed a nonsense mutation, and a Dutch family displayed a 1.

Molecular anthropology meets genetic medicine to treat blindness in the North African Jewish population: human gene therapy initiated in Israel.

The history of the North African Jewish community is ancient and complicated with a number of immigration waves and persecutions dramatically affecting its population size. A decade-long process in Israel of clinical-molecular screening of North African Jews with incurable autosomal recessive blindness led to the identification of a homozygous splicing mutation (c.95-2A > T; IVS2-2A > T) in RPE65, the gene encoding the isomerase that catalyzes a key step in the retinoid-visual cycle, in patients from 10 unrelated families.

Novel null mutations in the EYS gene are a frequent cause of autosomal recessive retinitis pigmentosa in the Israeli population.

Purpose: To characterize the role of EYS, a recently identified retinal disease gene, in families with inherited retinal degenerations in the Israeli and Palestinian populations.

Methods: Clinical and molecular analyses included family history, ocular examination, full-field electroretinography (ERG), perimetry, autozygosity mapping, mutation detection, and estimation of mutation age.

Results: Autozygosity mapping was performed in 171 consanguineous Israeli and Palestinian families with inherited retinal degenerations.