Table 1.
Clinical, genetic, and imaging characteristics of patients with genetically confirmed adult-onset PLAN in the literature
| Author, year | Patient | Ethnicity | Genotype | Type | Sex | AAO | Initial symptoms | Main symptoms during examination | MRI | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EPS | Dystonia | Pyramidal signs | Ataxia | Psychiatric | |||||||||
| Homozygous p.D331Y mutations (N = 5) | |||||||||||||
| Shi et al. 2011 [6] | P1 | Chinese | Homo c.991G > T (p. D331Y) | EOPD | M | 37 | Gait disturbance | + | – | – | – | – | nl |
| Xie et al. 2015 [7] | PA | Chinese | Homo c.991G > T (p. D331Y) | EOPD | M | 36 | Gait disturbance | + | – | – | – | – | nl |
| PB | Chinese | Homo c.991G > T (p. D331Y) | EOPD | M | 36 | Right hand tremor | + | – | – | – | – | nl | |
| This study | P2 | Chinese | Homo c.991G > T (p. D331Y) | EOPD | F | 30 | Slowing gait | + | – | – | – | D, P, A | nl |
| P3 | Chinese | Homo c.991G > T (p. D331Y) | EOPD | F | 26 | Right leg clumsiness | + | – | + | – | D, A | nl | |
| Compound heterozygous p.D331Y/ other mutations (N = 5) | |||||||||||||
| Lu et al. 2012 [8] | P3 | Chinese | Compound hetero c.991G > T (p. D331Y)/c.1077G > A (M358IfsX) | DP | F | 19 | Unsteadiness and bradykinesia | + | + | – | + | P,C | CoA, CeA |
| Chen et al. 2018 [9] | P3 | Chinese | Compound hetero c.991G > T(p.D331Y)/c.1982C > T | DP | M | 29 | Walking difficulty | + | – | – | + | – | CeA |
| P4 | Chinese | Compound hetero c.991G > T(p.D331Y)/ c.2218G > A (p.G740R) | HSP | F | 31 | Gait disturbance | – | – | + | + | – | CeA | |
| Ji et al. 2019 [10] | P1 | Chinese | Compound hetero c.991G > T (D331Y)/c.1648delC | Ataxia | F | 30 | Imbalance | – | – | + | + | D | CeA |
| This study | P1 | Chinese | Compound hetero c.991G > T (p. D331Y)/c.1077G > A (M358IfsX) | DP | M | 18 | Depression and psychosis | + | + | – | – | D, P, C | CoA, CeA |
| Homozygous Mutations other than p.D331Y (N = 17) | |||||||||||||
|
Paisa’n-Ruiz et al., 2008 [3] |
P1 of F1 | Indian | Homo c.2222G > A (p.R741Q) | DP | F | 26 | Cognitive decline | + | + | + | – | D, C | CoA |
| P1 of F2 | Pakistani | Homo c.2239C > T (p.R747W) | DP | F | 18 | Foot drag | + | + | + | – | C | CoA | |
| Sina et al. 2009 [11] | P1 | Iranian | Homo c.C1894T (p.R632W) | DP | M | 25 | Foot drag | + | + | + | – | C | CoA |
| P2 | Iranian | Homo c.C1894T (p.R632W) | DP | M | 22 | Foot drag | + | + | + | – | C | CoA | |
| P3 | Iranian | Homo c.C1894T (p.R632W) | DP | F | 21 | Foot drag | + | + | + | + | C | CoA | |
| Agarwal et al., 2012 [12] | P1 | Scandinavian | Homo c.G238A (p.A80T) | EOPD | F | 22 | Depression | + | + | + | – | D, A, C | I |
| Virmani et al., 2014 [13] | P1 | Indian | Homo c.2222G > A (p.R741Q) | DP | F | 25 | Depression and psychosis | + | + | + | – | D, P | CoA |
| P2 | Indian | Homo c.2222G > A (p.R741Q) | DP | F | 22 | Depression | + | + | + | – | – | CoA | |
|
Malaguti et al. 2015 [14] |
P | Italian | Homo c.C1547T (p.A516W) | DP | F | 27 | Stiff leg sensation | + | + | + | – | C | I |
| Giri et al. 2016 [15] | P | Turkish | Homo c.2239C > T (p.R747W) | EOPD | F | 27 | Left limb slowness | + | – | – | – | D,P,C | CoA |
| Ozes et al. 2017 [16] | P2 | Turkish | Homo c.2239C > T (p.R747W) | HSP | M | 21 | Scissoring gait | – | – | + | + | – | I |
| Koh et al. 2018 [17] | D II-3 | Japanese | Homo c.1904G > A (p.R635Q) | HSP | F | 66 | Gait impairment | + | – | + | – | – | nl |
|
Bohlega et al. 2018 [18] |
P1 of F1 | Saudi Arabian | Homo c.2222G > A (p.R741Q) | EOPD | F | 26 | Depression, bradykinesia | + | – | + | – | D, C | CoA |
| P2 of F1 | Saudi Arabian | Homo c.2222G > A (p.R741Q) | EOPD | M | 22 | Depression, tremor | + | – | + | – | D, C | CoA | |
| P3 of F1 | Saudi Arabian | Homo c.2222G > A (p.R741Q) | EOPD | F | 23 | Bradykinesia | + | – | + | – | C | CoA | |
| P1 of F2 | Saudi Arabian | Homo c.2222G > A (p.R741Q) | EOPD | M | 25 | Cognitive decline | + | – | + | – | C | CoA | |
| Rohani et al. 2018 [19] | P | Saudi Arabian | Homo p. Ala681Cysfs*92 | DP | M | 18 | Bradykinesia, tremor | + | + | + | – | P | nl |
| Compound Heterozygous mutations other than p.D331Y (N = 8) | |||||||||||||
| Yoshino et al. 2010 [20] | PA | Japanese | Compound hetero c.C216A (p. p.F72L) /c.G1904A (p.R635Q) | EOPD | F | 20 | Resting tremor, unsteady gait | + | – | – | – | D,P,C | CoA, I |
| PB1 | Japanese | Compound hetero c.C1354T (p.Q452X) /c.G1904A (p.R635Q) | EOPD | M | 25 | Bradykinesia, gait disturbance | + | – | – | – | C | CoA | |
| PB2 | Japanese | Compound hetero c.C1354T (p.Q452X) /c.G1904A (p.R635Q) | EOPD | M | 30 | Bradykinesia, gait disturbance | + | – | – | – | P,C | CoA | |
| Bower et al., 2011 [21] | P1 | European | Compound hetero c.C4A (p.Q2K)/Del Ex 3 (pL71_S142del) | DP | F | 18 | Depression | + | + | + | – | D | GP |
| Kim et al. 2015 [22] | P1 | Korean | Compound hetero c.G1039A (p.G347R) /c.C1670T (p.S557L) | DP | F | 22 | Unsteady gait and falls | + | + | + | + | C | CeA, I |
|
Wirth et al. 2017 [23] |
P1 | Caucasian | Compound hetero c.109C > T (p.R37X)/ c.2321G > T (p.Ser774Iso) | EOPD | M | 23 | Depression and anxiety | + | + | – | – | D,P,A | nl |
| P2 | Caucasian | Compound hetero c.758G > T (Gly253Val)/c.2341G > A (Ala781Thr) | EOPD | M | 27 | Left leg tremor and anxiety | + | – | + | – | P,A,C | nl | |
| Chen et al.2018 [9] | P2 | Chinese | Compound heteroc.668C > T (p.P223L) /c.1915G > A(p.A639T) | EOPD | M | 27 | Walking difficulty | + | – | + | – | – | CeA, GP, I |
Abbreviations: +, present; −, absent or not reported; F1 family 1; P1 patient 1; DP dystonia-parkinsonism; EOPD early-onset Parkinson’s disease; HSP hereditary spastic hemiplegia; AAO age at onset; EPS extrapyramidal sign; MRI magnetic resonance imaging; D depression; P psychosis; A anxiety; C cognitive decline; CoA Cortical atrophy; CeA Cerebellar atrophy; GP T2- hypointensity in globus pallidus; I Iron accumulation; nl normal; hypo hypometabolism; NA not available