Clinical description and genome wide linkage study of Y-sutural cataract and myopia in a Chinese family.
Clinical description and genome wide linkage study of Y-sutural cataract and myopia in a Chinese family.
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发表时间：
2004-11
期刊：
影响因子：
2.2
通讯作者：
Qingjiong Zhang;Xiangming Guo;Xueshan Xiao;Junhui Yi;Xiao-yun Jia;J. Hejtmancik
中科院分区：
文献类型：
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作者：
Qingjiong Zhang;Xiangming Guo;Xueshan Xiao;Junhui Yi;Xiao-yun Jia;J. Hejtmancik
目的 描述一个中国大家庭中与近视相关的 Y 缝白内障的临床特征，并确定致病基因和突变。方法 在中国南方的一个汉族大家庭的成员中发现了常染色体显性 Y 缝白内障和近视。进行了眼科检查并记录了病史。采集血样用于 DNA 分离。使用间隔约 10 cM 的标记进行基因组范围扫描，以进行基因分型和两点连锁分析。对候选基因进行了测序。结果 双侧晶状体混浊是儿童早期白内障的唯一症状，也是所有受影响个体中最显着的症状，涉及整个前 Y 形缝合线和后倒 Y 形缝合线，呈现鸡毛掸子状外观。该家族中的 Y 缝白内障映射到染色体 3q22 上 D3S3606 和 D3S1309 之间的 11.4 cM (13.5 Mb) 区域，D3S1292 在 theta=0 处的最大 lod 得分为 5.7。对珠状丝结构蛋白 2 (BFSP2) 基因的序列分析发现了先前描述的 c.697_699delGAA (E233del) 突变，该突变存在于所有 Y 缝状白内障个体中，但不存在于未受影响的个体和对照中。在 12 名白内障患者中观察到 10 名近视，显着高于未受影响的后代和兄弟姐妹（8 名中的 1 名），独立映射到 3q21.3-q27.2 上 D3S3606 和 D3S1262 之间的 61.2 cM (59 Mb) 区域，最大 lod 得分为 3.79。结论 这种 Y 缝白内障是由 BFSP2 中的 E233del 突变引起的，这提供了支持 BFSP2 突变作为白内障原因的额外证据，并证明了 BFSP2 引起的白内障的表型变异。晶状体 Y 缝混浊可能是 BFSP2 突变引起的白内障的典型且最早的体征。此外，这些结果表明该区域存在近视易感位点，这也可能与BFSP2的突变有关。
PURPOSE To describe the clinical characteristics of a Y-sutural cataract associated with myopia in a large Chinese family and to identify the causative gene and mutation. METHODS An autosomal dominant Y-sutural cataract and myopia were identified in members of a large family of Han ethnicity living in southern China. Ophthalmological examinations were performed and a medical history was taken. Blood samples were collected for DNA isolation. A genome wide scan was performed using markers spaced at about 10 cM intervals for genotyping and two point linkage analysis. Candidate genes were sequenced. RESULTS Bilateral lens opacities, the only sign of cataract in early childhood and the most prominent sign in all affected individuals, involved the entire anterior Y and posterior inverted Y sutures, showing a feather duster like appearance. The Y-sutural cataract in this family mapped to an 11.4 cM (13.5 Mb) region between D3S3606 and D3S1309 on chromosome 3q22 with a maximum lod score of 5.7 at theta=0 for D3S1292. Sequence analysis of the beaded filament structural protein 2 (BFSP2) gene identified a previously described c.697_699delGAA (E233del) mutation which was present in all individuals with Y-sutural cataract but not in unaffected individuals and controls. Myopia, observed in 10 out of 12 cataract patients and significantly higher than that in unaffected offspring and siblings (1 out of 8), was independently mapped to a 61.2 cM (59 Mb) region between D3S3606 and D3S1262 on 3q21.3-q27.2 with maximum lod score of 3.79. CONCLUSIONS This Y-sutural cataract is caused by an E233del mutation in BFSP2 which provides additional evidence supporting mutations in BFSP2 as a cause for cataract and demonstrates phenotypic variability in cataracts caused by BFSP2. The Y-sutural opacity in the lens might be the typical and earliest sign for cataract caused by the BFSP2 mutation. In addition, these results demonstrate a myopia susceptibility locus in this region, which might also be associated with the mutation in BFSP2.