PRKN Variant Carrier Tables And Clinical Characteristics
PRKN Variant Table Continuation
| Visible locus / allele | rsID | cDNA / protein | Variant call | Annotation / ClinVar | Visible comment |
|---|---|---|---|---|---|
| 16156 / 9381 | rs766948045 | coding_sequence_variant, missense_variant, non_coding_transcript_variant | not reported | ||
| 16156 / 9384 | rs755749488 | missense_variant, coding_sequence_variant, non_coding_transcript_variant | not reported | ||
| 16178 / 5820 / G.A | rs34424986 | c.823C > T (p.Arg275Trp) | deleterious miss | Missense variant, pathogenic; missense_variant, non_coding_transcript_variant, synonymous_variant, coding_sequence_variant; pathogenic | Hetero PD 118명 vs Hetero control 6명 (no homo) |
| 16178 / 5885 | rs747427602 | c.758G > A (p.Cys253Tyr) | deleterious miss | non_coding_transcript_variant, coding_sequence_variant, missense_variant; pathogenic | Hetero 만 1명! |
| 16205 / 4156 | |||||
| 16226 / 2626 | |||||
| 16226 / 2743 | |||||
| 16244 / 3356 | |||||
| 16244 / 3371 | |||||
| 16205 / 4176 | |||||
| 16226 / 5190 | rs556724953 | splice_donor_variant | intron_variant; Not Reported in ClinVar | ||
| 16227 / 1417 | |||||
| 16227 / 4974 / G.A | rs9364644 | NA | pLoF, splice_donor_variant | Search by "6": 162864412 C > T -> intron_variant: 59%; NMD_transcript_variant: 24%; non_coding_transcript_variant: 12%; splice_donor_variant: 6%; rs9364644 | 'Not Reported' in ClinVar, but protein truncation variants (pPTVs) by VEP HC (근데 내가 왼쪽에 조사한 결과와 다르네?) -> 이기 임상에 포함해야 하나? Hetero PD 41명 vs Hetero control 24명 (no homo at all) |
| 16244 / 3325 | rs1292308780 | frameshift_variant | non_coding_transcript_variant, coding_sequence_variant, synonymous_variant, intron_variant, missense_variant | not reported | |
| 16244 / 3378 |
N LoF + Deleterious Missense Carriers (AMP-PD)
N LoF + Deleterious missense carriers (AMP-PD)
:2666 (Unrelated Caucasians)
- PD=1272,
- HC=794,
- Others (genetic cohort, other disease, prodromal PD)=600
LoFs are detected by VEP LOFTEE (HC)
Deleterious missense are detected by Helix (version: before Nov 2020 update)
| ID | Homo_PD | Hetero_PD | Homo_HealthyControl | Hetero_HealthyControl | Homo_Others | Hetero_Others | Annotation / consequence |
|---|---|---|---|---|---|---|---|
| RKN_chr6.161350160.C.G | 0 | 1 | 0 | Deleterious Miss. | |||
| RKN_chr6.161350187.G.A | 1 | 7 | 0 | Deleterious Miss. | |||
| RKN_chr6.161350208.C.T | 0 | 1 | 0 | Deleterious Miss. | |||
| RKN_chr6.161360169.G.A | 0 | 4 | 0 | Deleterious Miss. | |||
| RKN_chr6.161569381.G.A | 0 | 0 | 0 | Deleterious Miss. | |||
| RKN_chr6.161569384.G.A | 0 | 1 | 0 | Deleterious Miss. | |||
| RKN_chr6.161785820.G.A | 0 | 11 | 0 | Deleterious Miss. | |||
| RKN_chr6.161785885.C.T | 0 | 1 | 0 | Deleterious Miss. | |||
| RKN_chr6.162054156.C.A | 0 | 0 | 0 | Deleterious Miss. | |||
| RKN_chr6.162262626.C.T | 0 | 0 | 0 | pLoF splice_acceptor_variant | |||
| RKN_chr6.162262743.C.T | 1 | 0 | 0 | pLoF splice_donor_variant | |||
| RKN_chr6.162443356.C.G | 0 | 1 | 0 | pLoF splice_donor_variant | |||
| RKN_chr6.162443371.G.A | 0 | 3 | 0 | pLoF splice_donor_variant | |||
| RKN_chr6.162054176.T.G | 0 | 0 | 0 | pLoF splice_donor_variant | |||
| RKN_chr6.162265190.T.A | 0 | 6 | 0 | pLoF splice_donor_variant | |||
| RKN_chr6.162271417.C.A | 0 | 1 | 0 | pLoF splice_donor_variant | |||
| RKN_chr6.162274974.G.A | 0 | 1 | 0 | pLoF splice_donor_variant | |||
| RKN_chr6.162274974.G.C | 0 | 41 | 0 | pLoF splice_donor_variant | |||
| RKN_chr6.162443325.D.1 | 0 | 1 | 0 | pLoF frameshift_variant | |||
| RKN_chr6.162443373.D.2 | 0 | 2 | 0 | pLoF frameshift_variant | |||
| pLoF_sum | 0 | 52 | 0 | 41 | 0 | 44 | |
| Deleterious miss._sum | 2 | 30 | 0 | 16 | 0 | 12 | |
| Total_sum | 2 | 82 | 0 | 57 | 0 | 56 |
Total, 197 LoF+D.miss carriers exist in AMP-PD cohort
Takeda Pharmaceutical Company Limited
Page, 2020 #1751
From 1500 cases, they found 199 Parkin mutant-PD
- 199 cases carried either homozygous (n = 92) or compound heterozygous (n = 59) PRKN mutations
Table 2. Demographic And Clinical Characteristics
TABLE 2. Demographic and Clinical Characteristics of Patients with Parkinson’s Disease with Pathogenic PRKN Variants (PRKN-PD) and of Patients without Pathogenic Variants (PD-NM)
| Characteristics | PD-NM n=1181 | PRKN-PD n=228 | p Value | Coefficient or odds ratio (OR) (SE) | Cohen's f2 | p Value |
|---|---|---|---|---|---|---|
| Baseline | ||||||
| Sex (% male) | 727/1,181 (61.6%) | 118/228 (51.8%) | 0.016 | |||
| Mean age at examination (SD), y | 50.5 (13.2) | 45.4 (12.9) | <0.0001 | |||
| Mean disease duration (SD), y | 8.8 (7.8) | 14.1 (10.4) | <0.0001 | |||
| Mean age at onset (SD), y | 41.6 (12.0) | 31.2 (10.7) | <0.0001 | |||
| L-DOPA-treated | 791/1,181 (67%) | 148/228 (64.9%) | 0.69 | |||
| Levodopa responsiveness | 659/738 (89.3%) | 142/149 (95.3%) | 0.045 | 1.9 (0.82) | 0.007 | 0.15 |
| Motor symptoms and signs | ||||||
| Dystonia at onset | 164/990 (16.6%) | 37/201 (18.4%) | 0.69 | 0.84 (0.18) | 0.001 | 0.46 |
| Akinesia at onset | 590/946 (61.3%) | 99/206 (48.1%) | 0.0010 | 0.51 (0.09) | 0.015 | 0.0003 |
| Tremor at onset | 570/960 (59.4%) | 142/205 (69.3%) | 0.021 | 1.7 (0.29) | 0.007 | 0.0076 |
| Micrographia | 308/927 (33.2%) | 42/204 (20.6%) | 0.0013 | 0.58 (0.11) | 0.007 | 0.010 |
| Asymmetry | 1,001/1,035 (96.7%) | 181/198 (91.4%) | 0.0049 | 0.26 (0.09) | 0.010 | 0.0005 |
| Bradykinesia | 1,033/1,069 (96.6%) | 201/208 (96.6%) | 1.0000 | 1.4 (0.63) | 0.002 | 0.46 |
| Rigidity | 1,008/1,066 (94.6%) | 194/204 (95.1%) | 0.90 | 1.1 (0.42) | <0.001 | 0.77 |
| Tremor | 796/1,056 (75.4%) | 168/205 (82%) | 0.057 | 1.5 (0.32) | 0.002 | 0.072 |
| Mean UPDRS III "ON" state (/108) (SD) | 19.6 (13.8) | 15.9 (11.9) | 0.0049 | -3.3 (1.2) | 0.008 | 0.014 |
| Mean Hoehn & Yahr "ON" state (/5) (SD) | 2 (0.91) | 2.00 (0.93) | 0.74 | -0.14 (0.09) | 0.003 | 0.16 |
| Dyskinesia | 457/667 (68.5%) | 97/178 (54.5%) | 0.0025 | 0.44 (0.09) | 0.020 | 0.0005 |
| Motor fluctuations | 485/663 (73.2%) | 82/177 (46.3%) | <0.0001 | 0.32 (0.07) | 0.041 | <0.0001 |
| Non-motor symptoms and signs | ||||||
| Dysautonomia | 254/470 (54.0%) | 36/192 (18.8%) | <0.0001 | 0.19 (0.05) | 0.095 | <0.0001 |
| Dementia | 67/667 (10.0%) | 6/153 (3.9%) | 0.037 | 0.34 (0.16) | 0.009 | 0.014 |
Data were expressed as mean (standard deviation) for continuous variables, and as counts (percentages) for categorical variables. We used t-tests to compare the two groups for continuous variables and Fisher’s exact tests for binary variables. Coefficients for continuous clinical features and odds ratios for binary clinical features and standard error (SE), Cohen’s f2 and p-values were calculated from GLMs with mutation status, sex, age at onset, disease duration, L-DOPA group and age at onset vs disease duration for all 15 variables except for onset variables for which only mutation status, sex and age-at-onset were added. Linear models were used for continuous variables; GLMs with logit links and Bernoulli distributions were used for binary variables; UPDRS III, the motor subsection of the Unified Parkinson’s Disease Rating Scale.
Levodopa responsiveness was defined as a >30% improvement in subjective perceived motor symptoms.
Uncertain Spans
- Upper PRKN variant table headers are not visible in this crop; the reconstructed table preserves visible cells only.
- Several rsID and transcript strings in the upper PRKN variant table are taken from crop-level OCR plus visual confirmation where legible; faint or cropped cells are left blank.
- Row-level right-side counts and consequence labels in the AMP-PD slide are too small to verify fully; aggregate rows are visually legible and retained.
- Superscript footnote letters in the article table are visible but not consistently legible; numeric values are retained without superscript letters where uncertain.