Table 1. Clinical features of families with alpha-synuclein (SNCA) mutations.

SNCA protein change	p.Ala30Pro 1	p.Glu46Lys 2	p.His50Gln 3	p.Gly51Asp 4, 5	p.Ala53Thr 6	p.Ala53Glu 7	p.Ala53Val 8	Duplication 9	Triplication 10	Double duplication 11
SNCA: 5′ start - ATG start -	177G>C c.88G>C	225G>A c.136G>A	239T>G c.150T>G12	241G>A c.152 G>A	246G>A c.157G>A	247C>A c.158C>A	247C>T c.158C>T	Whole gene copy number	Whole gene copy number	Whole gene copy number
Zygosity	Heterozygous	Heterozygous	Heterozygous	Heterozygous	Heterozygous	Heterozygous	Homozygous/ heterozygous	Gene duplication on one allele	Gene triplication on one allele	Gene duplication on both alleles
Clinical phenotype	Classic PD	Dementia with Lewy bodies phenotype	Classic PD	Severe PD with some patients with MSA features	Severe PD with some patients with MSA features	Severe PD with some patients with MSA features	Homozygous = PD Heterozygous = cognitive decline or psychosis	Usually classic PD, some with severe cognitive and frontal dementia 13	Severe PD with some patients with MSA features	Severe PD
Family	German 14	Spanish Basque Country 15	English 16	British 4, French 17, and Japanese 18	Large Sicilian (Contursi) kindred 6 and Greek 19, Swedish 20, Korean 21	Finnish 22	Japanese 23	French 24, Italian 25, Japanese 26, 27, Korean 28, Swedish 29, UK, Welsh 13	Spellman- Muenter (Iowa) kindred 30, Swedish 9	Pakistani 31
Estimated penetrance/ risk	71.4%	30%	30% Heterozygous ExAc =4/121,306	100%	85%	100%	Homozygous 100% Heterozygous on ExAc = 1/121,304	44% 27	100%	100%
Mean age of onset, years	60	50–65	71	44 (as early as 19) 5	48	43	59	50	40	31
Clinical symptoms	Progressive parkinsonism, walking difficulties, no other non-motor symptoms except cognitive decline (50% of patients)	Resting tremor, bradykinesia, postural instability, severe immobility, dementia, and visual hallucinations	Resting hand tremor, benign course	Resting tremor, dystonia, cognitive/frontal decline, anxiety, depression, visual hallucination, and autonomic disturbances 5	Moderate tremor, rigidity, bradykinesia, postural instability, severe dementia, depression, and autonomic disturbance 32	Bradykinesia, resting tremor, rigidity, insomnia, spasticity, myoclonic jerks, anxiety, and panic disorders	Bradykinesia, resting tremor, rigidity, mild cognitive decline, visual hallucination, sleep disorder, delusions, and paranoia	Bradykinesia, resting tremor, rigidity, mild asymmetric onset. Some have epilepsy, depression, and frontal dementia.	Severe early onset parkinsonism, resting tremor, bradykinesia, rigidity, and symptoms of MSA	Severe bilateral bradykinesia rigidity, mild resting tremor, severe depression, and postpartum psychosis
Sustained response to levodopa	Transient marked, developed hallucinations	Mild to moderate, developed hallucinations and conscious fluctuation	Moderate	Transient marked, developed choreiform movements	Marked	Marked, developed dyskinesia 33	Marked	Mild to moderate, developed motor fluctuation and dyskinesia	Marked	N/A

ExAC, http://exac.broadinstitute.org; MSA, multiple system atrophy; N/A, no data available; PD, Parkinson’s disease; SNCA, alpha-synuclein gene.