Congenital motor nystagmus linked to Xq26-q27
Congenital motor nystagmus linked to Xq26-q27
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DOI：
10.1086/302244
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发表时间：
1999-02-01
影响因子：
9.8
通讯作者：
Maumenee, LH
中科院分区：
文献类型：
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作者：
Kerrison, JB;Vagefi, MR;Maumenee, LH
先天性运动性眼球震颤 (CMN) 是一种遗传性疾病，其特征是在出生后 6 个月内开始出现双侧眼球震颤。它必须与那些遗传性疾病（例如眼白化病（OA）、先天性静止性夜盲症（CSNB）和蓝锥体单色盲（BCM））区分开来，在这些遗传性疾病中，眼球震颤伴随着临床上明显的视觉感觉系统缺陷。尽管 CMN 被认为是由注视神经异常引起的，但尚不清楚分子缺陷是位于眼睛还是大脑。它可能以常染色体显性、常染色体隐性或 X 连锁模式遗传。通过连锁和候选基因分析对三个以 X 连锁、不规则显性模式遗传的 CMN 家族进行了研究。女性专性携带者的外显率为 54%。对 X 连锁 OA、CSNB 和 BCM 基因区域标记的评估未发现连锁证据，支持 CMN 代表不同实体的假设。该基因被定位到染色体 Xq26-q27，具有以下标记：GATA172D05（LOD 得分 3.164；重组分数 θ = 0.156）、DXS1047（LOD 得分 10.296；theta = 0）、DXS1192（LOD 得分 8.174；theta = 0.027）、DXS1232 （LOD 分数 6.015； theta = 0.036）、DXS984（LOD 分数 6.695；theta = 0）和 GATA31E08（LOD 分数 4.940；theta = 0.083）。单倍型评估和多点连锁分析给出的最大 LOD 得分为 10.790，1-LOD 单位支持间隔跨度类似于 7 cM，将该基因置于 GATA172D05 和 DXS1192 之间的区域。对候选基因 CDR1 和 SOX3 的评估并未发现受影响的男性受试者发生突变。
Congenital motor nystagmus (CMN) is a hereditary disorder characterized by bilateral ocular oscillations that begin in the first 6 mo of life. It must be distinguished from those genetic disorders-such as ocular albinism (OA), congenital stationary night blindness (CSNB), and blue-cone monochromatism (BCM)-in which nystagmus accompanies a clinically apparent defect in the visual sensory system. Although CMN is presumed to arise from a neurological abnormality of fixation, it is not known whether the molecular defect is located in the eye or in the brain. It may be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern. Three families with CMN inherited in an X-linked, irregularly dominant pattern were investigated with linkage and candidate gene analysis. The penetrance among obligate female carriers was 54%. Evaluation of markers in the region of the genes for X-linked OA, CSNB, and BCM revealed no evidence of linkage, supporting the hypothesis that CMN represents a distinct entity. The gene was mapped to chromosome Xq26-q27 with the following markers: GATA172D05 (LOD score 3.164; recombination fraction [theta] = 0.156), DXS1047 (LOD score 10.296; theta = 0), DXS1192 (LOD score 8.174; theta = 0.027), DXS1232 (LOD score 6.015; theta = 0.036), DXS984 (LOD score 6.695; theta = 0), and GATA31E08 (LOD score 4.940; theta = 0.083). Assessment of haplotypes and multipoint linkage analysis, which gave a maximum LOD score of 10.790 with the 1-LOD-unit support interval spanning similar to 7 cM, place the gene in a region between GATA172D05 and DXS1192. Evaluation of candidate genes CDR1 and SOX3 did not reveal mutations in affected male subjects.