Identification of a novel compound heterozygous CYP4V2 variant in a patient with autosomal recessive retinitis pigmentosa.
Identification of a novel compound heterozygous CYP4V2 variant in a patient with autosomal recessive retinitis pigmentosa.
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常染色体隐性遗传色素性视网膜炎患者中新型复合杂合 CYP4V2 变异的鉴定
DOI：
10.3892/br.2022.1523
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发表时间：
2022-05
影响因子：
2.3
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Zou T;Wang T;Zhen F;Dong S;Gong B;Zhang H
视网膜色素变性（RP）属于视网膜疾病家族，其特征在于视杆和视锥光感受器的进行性变性。本研究的目的是在一个非血缘关系的中国非综合征型常染色体隐性遗传性RP家系中筛选可能致病的遗传变异。对受影响个体（先证者）和先证者两个孩子的样本进行全外显子组测序（WES）。通过WES鉴定了细胞色素P450家族4亚家族V成员2（CYP4V2）基因中c.C958T（p.R320X）和c.G1355A（p.R452H）的一种新的复合杂合变体。随后，通过直接桑格测序验证该变体。发现这种复合杂合变异在其他未受影响的家族成员和400名种族匹配的健康对照个体中不存在。此外，该复合变体以常染色体隐性方式与RP表型共分离。计算机模拟分析显示，c.C958T（p.R320X）和c.G1355A（p.R452H）均可损害CYP4V2的蛋白功能。这些结果强烈表明该化合物变体是一种致病变体，其扩展了目前已知的与视网膜疾病相关的CYP4V2遗传变体的谱。
Retinitis pigmentosa (RP) belongs to a family of retinal disorders that is characterized by the progressive degeneration of rod and cone photoreceptors. The aim of the present study was to screen for possible disease-causing genetic variants in a non-consanguineous Chinese family with non-syndromic autosomal recessive RP. Whole-exome sequencing (WES) was performed in samples from the affected individual (the proband) and those from the two children of the proband. A novel compound heterozygous variant of c.C958T (p.R320X) and c.G1355A (p.R452H) in the Cytochrome P450 family 4 subfamily V member 2 (CYP4V2) gene was identified through WES. Subsequently, this variant was validated by direct Sanger sequencing. This compound heterozygous variant was found to be absent from other unaffected family members and 400 ethnically-matched healthy control individuals. In addition, this compound variant was co-segregated with the RP phenotype in an autosomal recessive manner. In silico analysis revealed that both c.C958T (p.R320X) and c.G1355A (p.R452H) could compromise the protein function of CYP4V2. These results strongly suggest this compound variant to be a disease-causing variant, which expands upon the spectrum of currently known CYP4V2 genetic variants associated with retinal diseases.
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影响因子：
3.9
作者：
Il, Lorenzo L. Nichols;Alur, Ramakrishna P.;Boobalan, Elangovan;Sergeev, Yuri V.;Caruso, Rafael C.;Stone, Edwin M.;Swaroop, Anand;Johnson, Mary A.;Brooks, Brian P.
通讯作者：
Brooks, Brian P.
锥杆营养不良中的 CRX 变异和突变概述
DOI：
10.1016/j.bbrc.2012.08.110
发表时间：
2012-10-05
影响因子：
3.1
作者：
Huang, Li;Xiao, Xueshan;Zhang, Qingjiong
通讯作者：
Zhang, Qingjiong
影响因子：
4
作者：
Lin, J;Nishiguchi, KM;Miyake, Y
通讯作者：
Miyake, Y
Bietti 结晶性角膜视网膜营养不良患者 CYP4V2 突变的鉴定和群体史
影响因子：
5.2
作者：
Jiao, Xiaodong;Li, Anren;Hejtmancik, J. Fielding
通讯作者：
Hejtmancik, J. Fielding
影响因子：
64.8
作者：
Badano, JL;Leitch, CC;Katsanis, N
通讯作者：
Katsanis, N