Molecular Genetics of 1α-Hydroxylase Deficiency in the Saudi Population.

PMID 41623903 | PMCID PMC12852950 | DOI 10.1210/jendso/bvaf183 · Journal of the Endocrine Society · 2026

CONTEXT: The aim of this study was to characterize the molecular genetics of 1α-hydroxylase deficiency in the highly consanguineous population of Saudi Arabia, hypothesizing that the results will show a unique CYP27B1 genotype. METHODS: We collected data on a large cohort of patients diagnosed with 1α-hydroxylase deficiency from different parts of the country. These patients underwent molecular testing for CYP27B1 mutations. RESULTS: A cohort of 45 patients from 29 unrelated families was studied. In 13 families (29 patients), more than one affected sibling was included (2-4 siblings) while the other 16 families had only a single patient per family. The patients included 24 females and 21 males with median age at time of presentation of 1 year and a current median age of 10 years. The clinical, biochemical and radiological profile was typical of 1α-hydroxylase deficiency. Molecular testing showed 10 mutations of different types in the 29 families. Four mutations were novel (p.(Trp257LeufsTer76), p.(Glu101Gln), p.(Gly398Ser), and p.(Arg206Cys)) while the other 6 mutations were previously described (p.(arg429Pro), p.(Phe443Profs*24), p.(Gln135Ter), p. (Gly102Glu), p.(Gln504Ter), and c.589 + 1G > A). Two of the previously reported mutations were from Saudi patients and have never been reported from other populations, increasing the number of novel/previously novel mutations to 6 of 10 mutations (60%). The most common mutation was c.1286G > C, p.(Arg429Pro) occurring in 22 patients from 15 unrelated families (51.7%). CONCLUSION: The molecular genetics of 1α-hydroxylase deficiency in Saudi Arabia is unique with several novel mutations of different types and a possible founder mutation.