Wong F, Goldberg M F, Hao Y
Department of Ophthalmology, Duke University School of Medicine, Durham, NC.
Arch Ophthalmol. 1993 Nov;111(11):1553-7. doi: 10.1001/archopht.1993.01090110119036.
Norrie's disease (ND) is a rare X-linked hereditary disorder characterized by congenital blindness. A putative gene for ND has been isolated and mapped to Xp11.3. Four point mutations in this gene have been identified recently in patients with ND, thus providing strong evidence that this gene is associated with the disease. We report a new mutation.
Clinical findings from the proband were correlated with results from DNA analysis. The proband's DNA was compared with that from his mother, an unaffected brother, and four unrelated normal males.
The proband was a male infant referred for ocular evaluation at 3 months of age.
The patient was evaluated with a general ocular examination at 4 months of age, a computed tomographic scan at 8 months of age, and then periodic follow-up examinations over the next 7 years. Blood samples were also collected from the proband, his family, and four unrelated normal males. DNA was extracted, amplified using polymerase chain reactions, and then cloned and sequenced.
RESULTS/CONCLUSIONS: We identified a new mutation at codon 128 of the ND gene, a dinucleotide GC-to-AA substitution that changed the normal codon for cysteine, TGC, to TAA, which is a stop codon. Thus, this patient lacks the last six amino acids of the carboxyl terminus of the ND protein. The normal ND protein has 11 cysteines in conserved positions that are proposed to be functionally significant. The mutation at codon 128 occurs at the 10th cysteine and might be expected to alter the function of the ND protein. Since the phenotype of this patient is similar to those of other patients with point mutations in the ND gene, this mutation is likely to be the molecular basis of the phenotype.
诺里病（ND）是一种罕见的X连锁遗传性疾病，其特征为先天性失明。一个推定的ND基因已被分离并定位于Xp11.3。最近在ND患者中已鉴定出该基因的四处点突变，从而提供了有力证据证明该基因与该疾病相关。我们报告了一个新的突变。
先证者的临床发现与DNA分析结果相关联。将先证者的DNA与他母亲、一位未患病的兄弟以及四名无关正常男性的DNA进行比较。
先证者是一名3个月大时因眼部评估前来就诊的男婴。
该患者在4个月大时接受了全面的眼部检查，8个月大时进行了计算机断层扫描，随后在接下来的7年中进行了定期随访检查。还从先证者及其家人以及四名无关正常男性身上采集了血样。提取DNA，使用聚合酶链反应进行扩增，然后进行克隆和测序。
结果/结论：我们在ND基因的第128密码子处鉴定出一个新突变，即二核苷酸GC到AA的替换，该替换将正常的半胱氨酸密码子TGC变为终止密码子TAA。因此，该患者缺乏ND蛋白羧基末端的最后六个氨基酸。正常的ND蛋白在保守位置有11个半胱氨酸，这些半胱氨酸被认为具有功能重要性。第128密码子处的突变发生在第10个半胱氨酸处，可能会改变ND蛋白的功能。由于该患者的表型与ND基因中其他点突变患者的表型相似，因此该突变很可能是该表型的分子基础。
