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.
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.
Wong F, Goldberg MF, Hao Y. Identification of a Nonsense Mutation at Codon 128 of the Norrie's Disease Gene in a Male Infant. Arch Ophthalmol. 1993;111(11):1553-1557. doi:10.1001/archopht.1993.01090110119036