Table 1.

Genes and cytogenetic locations in hereditary forms of Parkinson’s disease their clinical phenotypes and neuropathological findings.

Gene symbol	Cytogenetic location	Gene name	Inheritance	Phenotype	Pathology
PARK1	4q21–23	SNCA	AD	“Contursi kindred”, typical Parkinson’s disease manifesting with two or more cardinal signs (bradykinesia, rigidity, tremor, postural instability and with early or young onset (EOPD, YOPD); in some cases, the cognitive disturbance, psychotic signs, hyperreflexia, spasticity, and myoclonus were recorded	Severe degree of LB pathology. The majority of cases present also neurofibrillary tangles. TDP-43 pathology in the hippocampus in some cases
PARK2	6q25.2–q27	Parkin	AR	Typical Parkinson’s disease manifesting with two or more cardinal signs (bradykinesia, rigidity, tremor, postural instability) and with the early onset (EOPD); hyperreflexia, feet dystonia, and prominent retropulsion and sensory axonal neuropathy were recorded	LB pathology of different degrees present in a minority of cases; different degrees of tau inclusions and particularly typical PSP pathology present in part of the cases
PARK3	2p13	Unknown	AD	Typical Parkinson’s disease manifesting with two or more cardinal signs (bradykinesia, rigidity, tremor, postural instability) and with the late onset as seen in “sporadic” disease	Brain pathology is not known
PARK4	4q21–23	SNCA	AD	“Iowa kindred”, typical Parkinson’s disease manifesting with two or more cardinal signs (bradykinesia, rigidity, tremor, postural instability) with early or young onset (EOPD, YOPD); cognitive disturbance and dysautonomia were also recorded	Severe degree of LB pathology. The majority of cases present also neurofibrillary tangles. TDP-43 pathology in the hippocampus in some cases
PARK5	4p13	UCHL1	AD	Typical Parkinson’s disease manifesting with two or more of cardinal signs (bradykinesia, rigidity, tremor, postural instability) and with young onset (YOPD)	Brain pathology is not known
PARK6	1p35–36	PINK1	AR	Typical Parkinson’s disease manifesting with two or more of cardinal signs (bradykinesia, rigidity, tremor, postural instability) and with asymmetric early onset (EOPD); in some cases the dystonia, hyperreflexia and sleep benefit were recorded	Limited data (only one published case with typical LB pathology)
PARK7	1p36.23	DJ1	AR	Typical Parkinson’s disease manifesting with two or more of cardinal signs (bradykinesia, rigidity, tremor, postural instability) and with asymmetric early onset (EOPD); in some cases the loss of postural reflexes, bulbar signs, and muscle atrophy were recorded	Limited data (only one published case with typical LB pathology)
PARK8	12q12–13.1	LRRK2	AD	Typical Parkinson’s disease manifesting with two or more of cardinal signs (bradykinesia, rigidity, tremor, postural instability) and with late onset; in some cases, prominent lateralization of symptoms was recorded	LB pathology with significantly heterogeneous distribution; similarly heterogeneous spread of tau inclusions of different types, TDP-43 pathology in the hippocampus in a minority of cases
PARK9	1p36.13	ATP13A2	AR	Kufor–Rakeb syndrome, early-onset (EOPD) atypical parkinsonism manifesting with bradykinesia, rigidity, prominent hypomimia, spasticity, supranuclear gaze palsy, and dementia; in some cases, facial mini-myoclonus, oculogyris crises and dystonia were recorded	Limited data (only one published case in which LB pathology was absent)
PARK10	1p32	Unknown	Unclear	Typical Parkinson’s disease manifesting with two or more cardinal signs (bradykinesia, rigidity, tremor, postural instability) and with the late onset as seen in “sporadic” disease	Brain pathology is not known
PARK11	2q37.1	GIGYF2	AD	Typical Parkinson’s disease manifesting with two or more cardinal signs (bradykinesia, rigidity, tremor, postural instability) and with the late onset as seen in “sporadic” disease	Brain pathology is not known
PARK12	Xq21–q25	Unknown	X-linked	Typical Parkinson’s disease manifesting with two or more cardinal signs (bradykinesia, rigidity, tremor, postural instability) and with the late onset as seen in “sporadic” disease	Brain pathology is not known
PARK13	2p13.1	HTRA2	AD	Typical Parkinson’s disease manifesting with two or more cardinal signs (bradykinesia, rigidity, tremor, postural instability) and with the late onset as seen in “sporadic” disease; with extremely positive and sustained response to L-DOPA therapy	Brain pathology is not known
PARK14	22q13.1	PLA2G6	AR	Atypical early-onset parkinsonian syndrome (young adulthood), with dominant tremor, bradykinesia, and rigidity, other features included rapid cognitive decline, dysarthria, supranuclear gaze palsy, eyelid opening apraxia, hyperreflexia and spasticity (PSP-like phenotype)	LB pathology of different degrees; in majority of cases were also neurofibrillary tangles present. Presence of iron accumulation
PARK15	22q12.3	FBX07	AR	Atypical early-onset parkinsonian syndrome with very slow progression, dominant bradykinesia and rigidity in most of cases accompanied by spasticity and hyperreflexia; the presence of Babinski sign and dystonia has been recorded. Atypical parkinsonism with PSP-P phenotype	Limited data (only one published case, in which the LB pathology with minor Alzheimer-type changes was present)a
PARK16	1q32	Unknown	Unclear	Typical Parkinson’s disease manifesting with two or more cardinal signs (resting tremor, bradykinesia, rigidity, postural instability) with the late onset as seen in “sporadic” disease and with more rapid motor progression	Brain pathology is not known
PARK17	16q11.2	VPS35	AD	Typical Parkinson’s disease manifesting with two or more cardinal signs (dominant resting tremor, bradykinesia, rigidity, postural instability) and with the late onset as seen in “sporadic” disease; cramps were present in some pedigrees Atypical parkinsonism with PSP-P phenotype	Limited data (only two published cases; in one case was the LB pathology absent, in other case was the LB pathology with minor Alzheimer-type changes present)a
PARK18	3q27.1	EIF4G1	AD	Typical late-onset Parkinson’s disease, asymmetric manifestation with resting tremor, bradykinesia, rigidity, postural instability, and with the long and mild progression	Brain pathology is not known
PARK19A/B	1p31.3	DNAJC6	AR	A: atypical juvenile-onset parkinsonism with dominant akinesia and rigidity, postural instability, dysarthria, dystonia, pyramidal signs, and occasional epileptic seizures and mental retardation B: typical early-onset Parkinson’s disease with resting tremor, bradykinesia, rigidity, and good response do L-DOPA	Brain pathology is not known
PARK20	21q22.1	SYNJ1	AR	Atypical early-onset parkinsonism with dominant akinesia and rigidity, postural instability, shuffling gait, supranuclear gaze palsy, apraxia of eyelid opening, staring gaze, dysarthria, dystonia, and cognitive decline	Brain pathology is not known
PARK21	20p13	TMEM230	AD	Typical Parkinson’s disease manifesting with resting tremor, bradykinesia, and rigidity; with the asymmetric onset and sustained response to L-DOPA therapy	Typical LB pathology, in some cases, were the tau inclusions typical for PSP present
PARK22	7p11.2	CHCHD2	AD	Typical Parkinson’s disease with bradykinesia, rigidity, and gait disturbance; with the asymmetric onset and sustained response to L-DOPA therapy	Brain pathology is not known
PARK23	15q22.2	VPS13C	AR	Atypical early-onset parkinsonism with dominant akinesia and rigidity, postural instability, early cognitive decline, dysautonomia, axial symptoms, pyramidal signs, and dysautonomia	Limited data (only one published case, in which typical LB pathology together with neurofibrillary tangles were present)
PARK24	10q22.1	PSAP	AD	Typical adult-onset Parkinson’s disease with resting tremor, bradykinesia and rigidity; asymmetric onset and sustained response to L-DOPA therapy	Brain pathology is not known

AD autosomal dominant, AR autosomal recessive, SNCA Synuclein Alpha, LRRK2 Leucin Rich Repeat Kinase2, PINK1 PTEN-Induced Putative Kinase 1, UCHL1 Ubiquitin Carboxyl-Terminal Hydrolase Isozyme L1, ATP13A2 ATPase 13A2, GIGYF2 GRB10 interacting GYF protein 2, HTRA2 Htr A serine peptidase 2, PLA2G6 phospholipase A2 group VI, FBX07 F-box protein 7, VPS35 VPS35 retromer complex component, EIF4G1 eukaryotic translation initiation factor, DNAJC6 DnaJ heat shock protein family (Hsp40), SYNJ1 synaptojanin 1, TMEM230 transmembrane protein 230, CHCHD2 coiled-coil–helix–coiled-coil–helix domain containing 2, VPS13C vacuolar protein sorting 13 homologue C, EOPD early-onset Parkinson’s disease (onset at the age <40 years according to the EPDA definition), YOPD young-onset Parkinson’s disease (onset at the age <50 years according to the APDA definition), PSP progressive supranuclear palsy, MSA multiple system atrophy. The gene names and cytogenetic locations correspond to the current data in the OMIM database (www.omim.org).

^aMensikova et al.⁵⁸.