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  • Whole-exome sequencing identified ARL2 as a novel candidate gene for MRCS (microcornea, rod-cone dystrophy, cataract, and posterior staphyloma) syndrome.

Whole-exome sequencing identified ARL2 as a novel candidate gene for MRCS (microcornea, rod-cone dystrophy, cataract, and posterior staphyloma) syndrome.

Clinical genetics (2019-04-05)
Xue-Bi Cai, Kun-Chao Wu, Xiao Zhang, Ji-Neng Lv, Guang-Hui Jin, Lue Xiang, Jie Chen, Xiu-Feng Huang, Deng Pan, Bin Lu, Fan Lu, Jia Qu, Zi-Bing Jin
초록

Adenosine diphosphate (ADP)-ribosylation factor-like 2 (ARL2) protein participates in a broad range of cellular processes and acts as a mediator for mutant ARL2BP in cilium-associated retinitis pigmentosa and for mutant HRG4 in mitochondria-related photoreceptor degeneration. However, mutant ARL2 has not been linked to any human disease so far. Here, we identified a de novo variant in ARL2 (c.44G > T, p.R15L) in a Chinese pedigree with MRCS (microcornea, rod-cone dystrophy, cataract, and posterior staphyloma) syndrome through whole-exome sequencing and co-segregation analysis. Co-immunoprecipitation assay and immunoblotting confirmed that the mutant ARL2 protein showed a 62% lower binding affinity for HRG4 while a merely 18% lower binding affinity for ARL2BP. Immunofluorescence images of ARL2 and HRG4 co-localizing with cytochrome c in HeLa cells described their relationship with mitochondria. Further analyses of the mitochondrial respiratory chain and adenosine triphosphate production showed significant abnormalities under an ARL2-mutant condition. Finally, we generated transgenic mice to test the pathogenicity of this variant and observed retinal degeneration complicated with microcornea and cataract that were similar to those in our patients. In conclusion, we uncover ARL2 as a novel candidate gene for MRCS syndrome and suggest a mitochondria-related mechanism of the first ARL2 variant through site-directed mutagenesis studies.

MATERIALS
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Sigma-Aldrich
Anti-UNC119 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
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SKUVendor SKU팩 크기재고 정보가격수량
EN300-1663499-50MG50 mg
Aldrich 제휴사로부터 14일 내에 출하
€349.20
EN300-1663499-100MG100 mg
Aldrich 제휴사로부터 14일 내에 출하
€498.70
EN300-1663499-250MG250 mg
Aldrich 제휴사로부터 14일 내에 출하
€692.40
EN300-1663499-500MG500 mg
Aldrich 제휴사로부터 14일 내에 출하
€1,064.20
EN300-1663499-1G1 g
Aldrich 제휴사로부터 14일 내에 출하
€1,352.80
EN300-1663499-2.5G2.5 g
Aldrich 제휴사로부터 14일 내에 출하
€2,608.60
EN300-1663499-5G5 g
Aldrich 제휴사로부터 14일 내에 출하
€3,838.40
EN300-1663499-10G10 g
Aldrich 제휴사로부터 14일 내에 출하
€5,671.40
Sigma-Aldrich
Anti-ARL2 (N-term) antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
로그인조직 및 계약 가격 보기
SKUVendor SKU팩 크기재고 정보가격수량
EN300-1663499-50MG50 mg
Aldrich 제휴사로부터 14일 내에 출하
€349.20
EN300-1663499-100MG100 mg
Aldrich 제휴사로부터 14일 내에 출하
€498.70
EN300-1663499-250MG250 mg
Aldrich 제휴사로부터 14일 내에 출하
€692.40
EN300-1663499-500MG500 mg
Aldrich 제휴사로부터 14일 내에 출하
€1,064.20
EN300-1663499-1G1 g
Aldrich 제휴사로부터 14일 내에 출하
€1,352.80
EN300-1663499-2.5G2.5 g
Aldrich 제휴사로부터 14일 내에 출하
€2,608.60
EN300-1663499-5G5 g
Aldrich 제휴사로부터 14일 내에 출하
€3,838.40
EN300-1663499-10G10 g
Aldrich 제휴사로부터 14일 내에 출하
€5,671.40