Identification of a novel GPR143 mutation in a large Chinese family with congenital nystagmus as the most prominent and consistent manifestation
Identification of a novel GPR143 mutation in a large Chinese family with congenital nystagmus as the most prominent and consistent manifestation
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DOI：
10.1007/s10038-007-0152-3
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发表时间：
2007-06-01
影响因子：
3.5
通讯作者：
Wang, Qing K.
中科院分区：
文献类型：
--
作者：
Liu, Jing Yu;Ren, Xiang;Wang, Qing K.
先天性眼球震颤的特点是一只或两只眼睛不自觉地、有节奏地反复振荡。我们研究了一个中国大家庭，其中9名患者的眼球震颤是一个突出和一致的表现表型，以绘制和鉴定眼球震颤的致病基因。家族中存在x连锁隐性遗传，9例患者中部分出现中央凹发育不全。该疾病基因定位于Xp22上一个约10.6 Mb的区域，该区域两侧为DXS996和DXS7593，具有显著的多点LOD评分峰值。对该区域21个候选基因的分析显示，GPR143（一种G蛋白偶联受体）的第二跨膜结构域出现了新的p.S89F突变，突变后可导致眼部白化病。家族中所有男性患者均为半合子突变；该突变的女性携带者是杂合的。在100名正常女性或100名正常男性中未发现p.S89F突变。我们的研究结果表明，GPR143基因的突变可导致一种变异形式的眼白化病，先天性眼球震颤是该中国家族所有患者中最突出且唯一一致的发现。这些结果扩大了与GPR143突变相关的临床表型谱。
Congenital nystagmus is characterized by involuntary, rhythmical, repeated oscillations of one or both eyes. We studied a large Chinese family with nystagmus as a prominent and consistent manifestation phenotype in nine patients to map and identify a disease-causing gene for nystagmus. X-linked recessive inheritance was observed in the family, and foveal hypoplasia was detected in some of the nine patients. The disease gene was mapped to an approximately 10.6 Mb region flanked by DXS996 and DXS7593 on Xp22 with a significant peak multipoint LOD score. Analysis of 21 candidate genes in the region revealed a novel p.S89F mutation in the second transmembrane domain of GPR143, a G protein-coupled receptor which causes ocular albinism when mutated. All male patients in the family were hemizygous for the mutation; the female carriers were heterozygous for the mutation. The p.S89F mutation was not identified in 100 normal females or 100 normal males. Our results indicate that a mutation in the GPR143 gene can cause a variant form of ocular albinism, with congenital nystagmus as the most prominent and only consistent finding in all patients in this Chinese family. These results expand the spectrum of clinical phenotypes associated with GPR143 mutations.