biostudies-literatureUnknown130(6)Lin CHMutations in the gene encoding the mitochondrial protein high temperature requirement A2 (HTRA2) are inconsistently associated with a risk of Parkinson's disease (PD). We assessed the presence of HTRA2 mutations among patients with PD and performed functional assay of identified mutations or variants. Among the total 1,373 subjects, the entire HTRA2 coding region was sequenced in 113 early-onset PD (EOPD), 20 familial PD patients and 150 control subjects. An additional 390 sporadic late-onset PD patients and 700 controls were subsequently screened to validate possible mutations found in the first set. We identified two novel heterozygous variants, c.427C > G (Pro143Ala) and c.906 +3 G > A, in 2 (1.5%) EOPD patients. The missense variant, Pro143Ala, was also observed in one late-onset PD paHuman genetics817-27https://www.ebi.ac.uk/biostudies/studies/S-EPMC3214265biostudies-literatureNovel variant Pro143Ala in HTRA2 contributes to Parkinson's disease by inducing hyperphosphorylation of HTRA2 protein in mitochondria.PMC3214265Wu RMChen GSTai CHChen MLLin CHfalseNovel variant Pro143Ala in HTRA2 contributes to Parkinson's disease by inducing hyperphosphorylation of HTRA2 protein in mitochondria.Mutations in the gene encoding the mitochondrial protein high temperature requirement A2 (HTRA2) are inconsistently associated with a risk of Parkinson's disease (PD). We assessed the presence of HTRA2 mutations among patients with PD and performed functional assay of identified mutations or variants. Among the total 1,373 subjects, the entire HTRA2 coding region was sequenced in 113 early-onset PD (EOPD), 20 familial PD patients and 150 control subjects. An additional 390 sporadic late-onset PD patients and 700 controls were subsequently screened to validate possible mutations found in the first set. We identified two novel heterozygous variants, c.427C > G (Pro143Ala) and c.906 +3 G > A, in 2 (1.5%) EOPD patients. The missense variant, Pro143Ala, was also observed in one late-onset PD pa2011-01-01T00:00:00Z2011 Dec2026-05-04T00:50:56.661Z2026-04-07T19:51:54.188ZS-EPMC32142652170178510.1007/s00439-011-1041-6