Molecular Analysis and Genetic Mapping of the Rhodopsin Gene in Families with Autosomal Dominant Retinitis Pigmentosa

Eighty-eight patients/families with autosomal dominant retinitis pigmentosa (RP) were screened for rhodopsin mutations. Direct sequencing revealed 13 different mutations in a total of 14 (i.e., 16%) unrelated patients. Five of these mutations (T4K, Q28H, R135G, F220C, and C222R) have not been reported so far. In addition, multipoint linkage analysis was performed on two large families with autosomal dominant RP due to rhodopsin mutations by using five DNA probes from 3q21-q24. No tight linkage was found between the rhodopsin locus (RHO) and D3S47 (θmax = 0.08). By six-point analysis, RHO was localized in the region between D3S21 and D3S47, with a maximum lod score of 13.447 directly at D3S20

Iduronate-2-sulfatase gene mutations in 16 patients with mucopolysaccharidosis type II (Hunter syndrome)

Mutations of the iduronate-2-sulfatase gene were identified in 16 patients with mucopolysaccharidosis type II (Hunter syndrome). Together with another 10 cases reported by us earlier it emerges that about 20% of the patients have deletions of the whole gene or other major structural alterations. One, two or three base pair deletions are found in about 23% of the cases while the remaining about 57% carry point mutations predicting amino acid replacement, premature termination of translation, or aberrant splicing. Molecular analysis of mRNA in splice site mutants showed that these latter defects frequently resulted in use of cryptic splice sites in exons or introns. 62% of the small deletions and point mutations have occurred in 3 of the 9 iduronate-2-sulfatase gene exons. Knowledge of the primary genetic defect allows fast and reliable carrier detection and prenatal diagnosis as well as insight into the relationship between genotype and phenotype