LSD genes and variants in the IPDGC cohort
Table 1. LSD genes and variants in the IPDGC cohort
| Disease | Gene | Variantsa |
|---|---|---|
| aglucosaminuria | AGA | 13 (10) |
| aromatic leukodystrophy | ARSA | 5 (5) |
| aux-Lamy disease | ARSB | 11 (10) |
| Lipogranulomatosis | ASAHI | 20 (17) |
| akeb syndrome | ATP13A2 | 24 (18) |
| al ceroid lipofuscinosis (CLN3) | CLN3 | 18 (17) |
| al ceroid lipofuscinosis (CLN5) | CLN5 | - |
| al ceroid lipofuscinosis (CLN6) | CLN6 | 10 (7) |
| al ceroid lipofuscinosis (CLN8) | CLN8 | 9 (4) |
| is | CTNS | 13 (12) |
| ialidosis | CTSA | 14 (11) |
| al ceroid lipofuscinosis (CLN10) | CTSD | 7 (4) |
| al ceroid lipofuscinosis (CLN13) | CTSF | 11 (9) |
| Pycnodysostosis | CTSK | 6 (5) |
| Neuronal ceroid lipofuscinosis (CLN4B) | DNAJC5 | 5 (5) |
| Fucosidosis | FUCA1 | 15 (12) |
| Pompe disease | GAA | 15 (10) |
| Krabbe disease | GALC | 36 (30) |
| Morquio A disease | GALNS | 22 (14) |
| Gaucher disease | GBA | 39 (32) |
| Fabry disease | GLA | 9 (7) |
| GM1-gangliosidosis/Morquio B | GLB1 | 8 (4) |
| GM2-gangliosidosis | GM2A | 1 (1) |
| I-Cell disease | GNPTAB | 39 (31) |
| Sanfilippo D syndrome | GNS | 20 (11) |
| Neuronal ceroid lipofuscinosis (CLN11) | GRN | 19 (12) |
| Sly disease | GUSB | 17 (10) |
| Tay-Sachs disease | HEXA | 20 (18) |
| Sandhoff disease | HEXB | 8 (6) |
| Sanfilippo C syndrome | HGSNAT | 18 (15) |
| Mucopolysaccharidosis type IX | HYAL1 | 13 (9) |
| Hunter syndrome | IDS | 9 (8) |
| Hurler syndrome | IDUA | 8 (4) |
| Neuronal ceroid lipofuscinosis (CLN14) | KCTD7 | 4 (3) |
| Danon disease | LAMP2 | 9 (7) |
| Wolman disease | LIPA | 14 (10) |
| Alpha-mannosidosis | MAN2B1 | 12 (11) |
| Beta-mannosidosis | MANBA | 18 (15) |
| Mucolipidosis type IV | MCOLN1 | 19 (14) |
| Neuronal ceroid lipofuscinosis (CLN7) | MFSD8 | 18 (14) |
| Schindler disease/Kanzaki disease | NAGA | 9 (8) |
| Sanfilippo B syndrome | NAGLU | 10 (9) |
| alidosis | NEU1 | - |
| Niemann-Pick disease type C1 | NPC1 | 43 (35) |
| Niemann-Pick disease type C2 | NPC2 | 2 (2) |
| Neuronal ceroid lipofuscinosis (CLN1) | PPT1 | 9 (7) |
| Sphingolipid-activator deficiency | PSAP | 22 (16) |
| action mycolonus-renal failure syndrome | SCARB2 | 10 (7) |
| Sanfilippo A syndrome | SGSH | 10 (8) |
| Sla disease | SLC17A5 | 18 (17) |
| Niemann-Pick disease type A/B | SMPD1 | 25 (21) |
| 3-gangliosidosis | ST3GAL5 | 11 (11) |
| tiple sulfatase deficiency | SUMF1 | - |
| Neuronal ceroid lipofuscinosis (CLN2) | TPP1 | 15 (13) |
a Number of variants (MAF < 3%) in each LSD gene is shown for the IPDGC discovery cohort, including total number of non-synonymous variants and likely damaging variants based on CADD (in parentheses). Of the 54 LSD genes considered, no genic variants in CLN5 or NEU1 passed quality control filters (see “Materials and Methods” section), and no non-synonymous variants were identified in SUMF1.
GPR37
Target
- Insoluble form of GPR37 has been reported to accumulate in the brains of AR-JP patients [9],
- mice lacking GPR37 are partially protected against dopaminergic cell death caused by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine [12].
- In SN (other regions?) of sPD (Braak stage 3-6): ↑ GRP37 protein (both overall & N-term cleaved form), ↑ GRP37 mRNA, in sPD
Genetic evidence
Strong
Bm
ecto-GPR37 as a potential PD biomarker
- ↑ amounts of ecto-GPR37 peptides in the CSF samples from PD patients
- PROCess
- To test if BM is to exist in CSF: immunoprecipitation with antibody → identification of the isolated peptides using LC-MS
- Assay development (ELISA, Species-specific) →
- measure in mouse CSF →
- measure in post-mortem human CSF (control & ↑ PD): small cohort →
- measure in post-mortem human CSF (control & ↑ PD): a larger and different cohort
: good ROC, but no correlation with disease severity
- No IVC
- No mechanistic study
Questions
- target vs bm
- ratification
- D-responsible neurodegeneration mechanism
Glossary
| E | WHV's post-transcriptional regulatory element Woodchuck Hepatitis Virus | Salk Institute scientists have identified cis-acting RNA elements from the Woodchuck Hepatitis Virus (WHV) that substantially increase the expression of transgenes delivered by retroviral vectors, in particular WHV's post-transcriptional regulatory element (WPRE). Insertion of specific WPRE in the 3′ untranslated region of coding sequences carried by either oncoretroviral or lentiviral vectors substantially increased levels of gene expression in a transgene-, promoter- and vector-independent manner |
|---|
H&Y (Hoehn and Yahr)
| Hoehn and Yahr Scale | Modified H and Y Scale | Median Time to Transit (Zhao et al. 2010, PMID 20213822) | Mean duration (accumulated) 2013 Kordower | Median time after stage 1- (Beaulieu-Jones, 2024 #2746) fig1과 suppl table 4,5과 좀 헷갈리게 상이 (아래는 fuppl table 5기준) | MDS-UPDRS total | MDS-UPDRS Motor (on state)(2013 Kordower?) | Putamen TH | Putamen DAT | SNc DA neuron | a-syn | SV2A | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| from previous stage (Months) | from stage 1 (year) | MGB : | HBS | ||||||||||
| nptoma | 4.7 y (Fearnley, 1991 #1529), 5y (Greffard... | ||||||||||||
| Unilateral involvement only usually with minimal or no functional disability | 14.4 (2017 Skorvanek) | at the onset of symptoms there was a 68% cell ... |
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
LSD genes IPDGC cohort table / disease names with leading consonants clipped | the leftmost disease-name column is partially clipped on the left edge throughout the table; visible characters preserved verbatim. | column truncation in source crop. |
GPR37 / Genetic evidence / Strong / Bm | the bullet labels read Genetic evidence, Strong, Bm; preserved verbatim though context suggests sub-headers. | low confidence on intended layout. |
H&Y table / second visible row beginning with nptoma | the first cell of the second data row begins with a clipped character preceding nptoma; preserved verbatim. | edge truncation. |
Hoehn and Yahr / 4.7 y (Fearnley, 1991 #1529), 5y (Greffard... | the Greffard reference is truncated mid-name; preserved verbatim. | source crop edge truncation. |