Genotype-Phenotype Correlation Reanalysis in 83 Chinese Cases with OCRL Mutations

Abstract

Background. Both Lowe syndrome and Dent-2 disease are caused by variants in the OCRL gene. However, the reason why patients with similar OCRL gene mutations presented with different phenotypes remains uncertain. Methods. Children with hemizygous pathogenic or likely pathogenic variants in OCRL were compiled from published and unpublished consecutive cases from China. Furthermore, a Chi-square test was employed to analyze the correlation of the location and types of mutations on the phenotype of children with Lowe syndrome or Dent-2 disease. Results. Among the total 83 patients, 70.8% (34/48) cases of Lowe syndrome presented with truncating mutations, while only 31.4% (11/35) cases of Dent-2 disease presented with truncating mutation (Χ2 = 12.662; P<0.001). Meanwhile, the majority of mutations in Dent-2 disease are located in Exon 2–12 (21/35, 60.0%), while the majority of mutations in Lowe syndrome are located in Exon 13–23 (39/48, 81.3%; Χ2 = 14.922; P<0.001). Conclusions. Truncating mutations of the OCRL gene were more common in patients with Lowe syndrome than in Dent-2 disease, while mutation is more likely located at exon 2–12 in Dent-2 disease than that in Lowe syndrome. The type and location of mutation are important indicators for the phenotypes in patients with OCRL mutation. This is a large cohort study analyzing the genotype-phenotype correlation in patients with Lowe syndrome and Dent-2 disease in China. Our data may improve the interpretation of new OCRL variants and genetic counseling. Furthermore, a large international study would be necessary to illustrate the genotype-phenotype correlation in patients with OCRL mutations.