Objective: To identify the pathogenic mutation underlying Lowe syndrome in a Chinese family.
Methods: After obtaining written informed consent of all participating individuals, peripheral blood samples were collected from 11 family members, including one affected male and three obligate female carriers, and an amniotic fluid sample was obtained from a pregnant carrier female in the family. Genomic DNA was extracted using the standard SDS-proteinase K-phenol/chloroform method. Linkage analysis was carried out using microsatellite markers flanking the OCRL gene. All OCRL exons and their flanking intronic sequences were PCR-amplified and sequenced for the proband. Restriction analysis was performed to confirm the pathogenic mutation. Prenatal genetic testing was carried out by combining haplotype analysis, DNA sequencing and restriction analysis.
Results: Linkage analysis showed that the affected male and three obligate carrier females shared a same haplotype. Sequence analysis in the proband revealed a nonsense mutation c.2032C→T (p.R678X) in exon 18 of the OCRL gene. Restriction analysis showed that the mutation was present in the proband and three obligate carriers, but not in the other 7 available family members. This nonsense mutation was not found in the amniotic fluid sample.
Conclusion: A recurrent OCRL nonsense mutation was found to be the pathogenic mutation in the Chinese family and the fetus didn't carry the mutation.