Recent interest has focused on the largest pedigree reported to date with histologically proven Lewy body parkinsonism with an autosomal-dominant mode of transmission.' It consisted of descendants of several immigrants to the United States linked to collateral Italian descendants by a common ancestor who had lived in the southern Italian town of Contursi during the late 18th century. The phenotype was characterized by a high penetrance (estimated at 85%), relatively early adult onset (age of onset varied from 28-68 yrs: mean, 46.5 ? 10.8 yrs), minimal tremor, and an aggressive progression (mean duration from onset to death of 9 years). The defective gene was mapped to chromosome 4q21-23.2 A single gene defect, identified as a single base pair change at position 209 from G to A (G209A) which results in an alanine to threonine substitution at position 53 (Ala53Thr) and the creation of a novel Tsp45 I restriction site, was located in exon 4 of the a-synuclein gene.' There was complete segregation between this mutation and the parkinsonian phenotype with one exception, in this Italian kindred. This mutation also segregated with the parkinsonian phenotype of an autosomal-dominant inheritance in three of five unrelated Greek families. This mutation was not present in any of their control subjects or in 52 Italian subjects with sporadic Parkinson's disease (PD). Our study aimed to answer whether this mutation existed in other populations, namely our control and sporadic PD subjects, mostly Chinese and a small number of British Caucasians.
Chinese subjects from Hong Kong (sporadic PD: 61 males, 57 females: control subjects without PD: 58 males, 66 females) and British Caucasians from Birmingham, U.K. (sporadic PD: 5 males, 4 females: control subjects without PD: 5 males, 5 females) were recruited. Sporadic PD was diagnosed in the presence of three of the following features: tremor, rigidity, bradykinesia, postural instability, and gait disturbance. Patients with a family history, atypical features, and parkinsonism resulting from any other neurologic diseases, chemicals, or toxins were excluded. The subjects were ethnically homogeneous