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AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration.

ABSTRACT: PURPOSE:To localize and identify the gene and mutations causing autosomal recessive retinal dystrophy in two consanguineous Pakistani families. METHODS:Consanguineous families from Pakistan were ascertained to be affected with autosomal recessive retinal degeneration. All affected individuals underwent thorough ophthalmologic examinations. Blood samples were collected, and genomic DNA was extracted using a salting out procedure. Genotyping was performed using microsatellite markers spaced at approximately 10 cM intervals. Two-point linkage analysis was performed with the lod score method. Direct DNA sequencing of amplified genomic DNA was performed for mutation screening of candidate genes. RESULTS:Genome-wide linkage scans yielded a lod score of 3.05 at ?=0 for D17S1832 and 3.82 at ?=0 for D17S938, localizing the disease gene to a 12.22 cM (6.64 Mb) region flanked by D17S1828 and D17S1852 for family 61032 and family 61227, which contains aryl hydrocarbon receptor interacting protein-like 1 (AIPL1), a gene previously implicated in recessive Leber congenital amaurosis and autosomal dominant cone-rod dystrophy. Sequencing of AIPL1 showed a homozygous c.773G>C (p.Arg258Pro) sequence change in all affected individuals of family 61032 and a homozygous c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. CONCLUSIONS:The results strongly suggest that the c.773G>C (p.R258P) and c.465G>T (p.(H93_Q155del)) mutations in AIPL1 cause autosomal recessive retinal degeneration in these consanguineous Pakistani families.

SUBMITTER: Li D

PROVIDER: S-EPMC3888496 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration.

Li David D Jin Chongfei C Jiao Xiaodong X Li Lin L Bushra Tahmina T Naeem Muhammad Asif MA Butt Nadeem H NH Husnain Tayyab T Sieving Paul A PA Riazuddin Sheikh S Riazuddin S Amer SA Hejtmancik J Fielding JF

Molecular vision 20140106

<h4>Purpose</h4>To localize and identify the gene and mutations causing autosomal recessive retinal dystrophy in two consanguineous Pakistani families.<h4>Methods</h4>Consanguineous families from Pakistan were ascertained to be affected with autosomal recessive retinal degeneration. All affected individuals underwent thorough ophthalmologic examinations. Blood samples were collected, and genomic DNA was extracted using a salting out procedure. Genotyping was performed using microsatellite marker ...[more]

PMID: 24426771

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Project description:BackgroundTo describe ocular manifestations, imaging characteristics, and genetic test results of autosomal recessive bestrophinopathy (ARB). The study design is an observational case series.MethodsForty-eight eyes of 24 patients diagnosed with ARB underwent complete ophthalmic examinations including refraction, anterior and posterior segment examination, enhanced depth imaging optical coherence tomography (EDI-OCT), fluorescein angiography (FA), electroretinography (ERG), and electrooculography (EOG). Optical coherence tomography angiography (OCTA) and BEST1 gene sequencing were performed in selected patients.ResultsThe age at onset was 4-35 years (mean: 18.6 years). The male-to-female ratio was 0.45. All patients were hyperopic, except one with less than one diopter myopia. EOG was abnormal in 18 cases with near-normal ERGs. Six patients did not undergo EOG due to their young age. Eighteen patients (75%) had a thick choroid on EDI-OCT, of which three had advanced angle-closure glaucoma, 15 patients were hyperopic, and eight of them had more than four diopters hyperopia in both eyes. Macular retinoschisis was observed in 46 eyes of 23 patients (95%) with cysts mostly located in the inner nuclear layer (INL) to the outer nuclear layer (ONL). Of the 18 patients who underwent FA, mild peripheral leakage was seen in eight eyes of four patients (22%). Subfoveal choroidal neovascularization (CNV) was seen in three eyes of two patients (6%) that responded well to intravitreal bevacizumab (IVB). Seven mutations of the bestrophin-1 (BEST1) gene were found in this study; however, only two of them (p.Gly34 = and p.Leu319Pro) had been previously reported as the cause of ARB based on ClinVar and other literature studies.ConclusionsARB can be presented with a wide spectrum of ocular abnormalities that may not be easily diagnosed. Pachychoroid can occur alongside retinal schisis and may be the underlying cause of angle-closure glaucoma in ARB. Our study also expands the pathogenic mutation spectrum of the BEST1 gene associated with ARB.

Dataset Information

AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration.

Publications

AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration.

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