Molecular analyses of GCH‐1, TH and parkin genes in Chinese dopa‐responsive dystonia families

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The symptomatic treatment of dopa-responsive dystonia (DRD) emphasizes the importance of molecular analyses of the GCH-1, TH and parkin genes. However, these analyses have not been extensively studied in Chinese DRD patients. Ten DRD families from the Han ethnic group including 14 patients and 28 clinically unaffected relatives were screened for GCH-1, TH and parkin mutations by direct sequencing, semiquantitative polymerase chain reaction (PCR), polymerase chain reaction-restriction fragment length polymorphism analysis and allele-specific PCR. Variations were verified in 200 unrelated control subjects. We have identified six novel mutations and three known mutations. The novel mutations are Leu91Val, Pro95Leu, Val204Gly and 628delC in GCH-1 gene; Gly216Ser in TH gene; and Cys253Phe in parkin gene. After molecular analyses of seven families with identified GCH-1 mutations, nine asymptomatic cases were found among 23 relatives, which confirmed the low penetrance of DRD. Unlike previous publications, male patients with GCH-1 mutations have early onset ages, while some female patients have very late onset ages in this medium-size series. Our data show that it is difficult to establish an evident genotype-phenotype correlation for DRD. However, it is necessary to know the genetic defects of DRD patients in clinics, which will help elucidate the mode of inheritance, facilitate causal therapy with levodopa and evaluate the prognosis.