Subject(s)
Chloride Channels/genetics , Genetic Diseases, X-Linked/genetics , Kidney Diseases/genetics , Phenotype , 5' Untranslated Regions/genetics , Adolescent , Adult , Child , Child, Preschool , Genetic Diseases, X-Linked/pathology , Humans , Infant , Kidney Diseases/pathology , Mutation/genetics , Polymorphism, Single-Stranded Conformational , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNAABSTRACT
We report the clinical and genetic study of a primary hyperoxaluria type I (PH1) family with two sisters homozygous for p.Gly170Arg who are still asymptomatic at age 29 and 35, and two brothers, also homozygous for the same mutation, who are affected since age 27 and 30. The clear sex difference observed in this family and in others reported in the literature fits well with the prevalence of males over females in the Italian registry. In the KO model of PH1, only male mice develop renal stones, suggesting that the sex difference may affect both oxalate production and stone formation. A likely mechanism is the sex-related expression of glycolate oxidase shown in experimental animals. The stable isotope method recently developed by Huidekoper and van Woerden for in vivo assessment of the endogenous oxalate production could help to clarify the issue in humans.
