Background: Classical homocystinuria (homocysteinemia type 1, MIM# 236200) is a rare inherited disorder in Mainland China. This study aimed to identify mutations in the cystathionine β-synthase (CBS) gene which are associated with classical homocystinuria in nine Chinese patients.
Methods: Nine Chinese patients were diagnosed at the age of 5 years 4 months to 18 years by plasma total homocysteine and blood methionine determination. CBS gene analysis was performed for the patients and their families.
Results: All nine patients had significantly increased plasma total homocysteine (142-500 μmol/L vs. the normal range of 0-15 μmol/L) and blood methionine (144.3-500 μmol/L vs. the normal range of 0-50 μmol/L). None of the patients was pyridoxine responsive. Eleven mutations in CBS gene were identified in the nine patients. Eight mutations (IVS3+1G>A, p.Thr493fsX46, p.Thr236Asn, p.Leu230Gln, p.Lys72Ile, p.Ser201ProfsX36, p.Met337IlefsX115, and IVS14-1G>C) were novel. Three mutations (p.Arg125Gln, p.Thr257Met and p.Gly116Arg) had been previously reported.
Conclusions: In this study, eight novel mutations in CBS were identified in nine Chinese patients with classical homocystinuria. None of the hotspot mutations reported in other regions previously was found. These data indicated that Chinese maybe had different CBS mutation spectrum from other population. The identification of mutations not only confirms the diagnosis but also enables accurate genetic counselling and prenatal diagnosis for the fetuses of the families.
Keywords: Cystathionine β-synthase; Homocysteine; Homocystinuria; Methionine; Mutation.