Liu Deyuan, Hu Zhengmao, Peng Yu, Yu Changhong, Liu Yalan, Mo Xiaoyun, Li Xiaoping, Lu Lina, Xu Xiaojuan, Su Wei, Pan Qian, Xia Kun
The State Key Laboratory of Medical Genetics of China, Central South University, ChangSha, China.
Mol Vis. 2010 Dec 8;16:2653-8.
Norrie disease (ND), a rare X-linked recessive disorder, is characterized by congenital blindness and, occasionally, mental retardation and hearing loss. ND is caused by the Norrie Disease Protein gene (NDP), which codes for norrin, a cysteine-rich protein involved in ocular vascular development. Here, we report a novel mutation of NDP that was identified in a Chinese family in which three members displayed typical ND symptoms and other complex phenotypes, such as cerebellar atrophy, motor disorders, and mental disorders.
We conducted an extensive clinical examination of the proband and performed a computed tomography (CT) scan of his brain. Additionally, we performed ophthalmic examinations, haplotype analyses, and NDP DNA sequencing for 26 individuals from the proband's extended family.
The proband's computed tomography scan, in which the fifth ventricle could be observed, indicated cerebellar atrophy. Genome scans and haplotype analyses traced the disease to chromosome Xp21.1-p11.22. Mutation screening of the NDP gene identified a novel nonsense mutation, c.343C>T, in this region.
Although recent research has shown that multiple different mutations can be responsible for the ND phenotype, additional research is needed to understand the mechanism responsible for the diverse phenotypes caused by mutations in the NDP gene.
诺里病（ND）是一种罕见的X连锁隐性疾病，其特征为先天性失明，偶尔伴有智力迟钝和听力丧失。ND由诺里病蛋白基因（NDP）引起，该基因编码诺里蛋白，一种参与眼部血管发育的富含半胱氨酸的蛋白质。在此，我们报告了在中国一个家族中鉴定出的一种新型NDP突变，该家族中有三名成员表现出典型的ND症状以及其他复杂表型，如小脑萎缩、运动障碍和精神障碍。
我们对先证者进行了全面的临床检查，并对其脑部进行了计算机断层扫描（CT）。此外，我们对先证者大家庭中的26名个体进行了眼科检查、单倍型分析和NDP基因DNA测序。
先证者的CT扫描显示第五脑室可见，提示小脑萎缩。基因组扫描和单倍型分析将该疾病追溯至X染色体p21.1 - p11.22区域。NDP基因的突变筛查在该区域鉴定出一个新的无义突变，c.343C>T。
尽管最近的研究表明多种不同突变可导致ND表型，但仍需要进一步研究以了解NDP基因突变导致多种表型的机制。
