GE/GMS Participant Mutation Table and MP-PD Parkin Variant Reanalysis

Preceding Application / Ethics Fragment

as well as other relevant stakeholders,
have been involved in the
development of the application and
plans for involvement in the proposed
research
 
appropriate ethical approval

GE/GMS Participant Mutation Table

Resource: mjff, fox-1, kondo-san,

Patient id	Primary indications	genotype / grouping	Mutations (focusing on tier 1 and tier 2 mutations)	hospital records related to PD/NS	Y of birth	year of registration	Y of death	ethnicity
1 (285)	Early onset and familial PD	CH	PRKN (tier 1, het frameshift, 6:162262560, hg38) PRKN (tier 2, het missense, 6:161350208, hg38) FOXP2 (tier 2)	(not checked)	1972	2016	-	White: British
2 (990) GMC	Early onset and familial PD	CH	PRKN (tier 1, het frameshift, 6:162443378, hg38) PRKN (tier 1, het stop-gained, 6:161785839, hg38) COQ8B, GALNS (tier 2)	(not checked)	1955	2017	-	(not stated)
3 (137)	Early onset dystonia	CH	PRKN (tier 1, het frameshift, 6:162201164, hg38) PRKN (tier 2, het missense, 6:161785793, hg38) SGCE (tier 2)	G249 (dystonia) G20 (PD)	1983	2017	-	(not stated)
4 (583) GMC	Early onset and familial PD	HOMOZ	PRKN (tier 1, hom frameshift, 6:162443378, hg38)	(not checked)	1960	2018	-	White: British
5 (506)	Early onset and familial PD	HOMOZ	PRKN (tier 1, hom frameshift, 6:162443378, hg38)	(not checked)	1966	2018	-	White: British
6 (880)	Early onset and familial PD	CH	PRKN (tier 1, het frameshift, 6:162262560, hg38) PRKN (tier 2, het missense, 6:161785820, hg38) ATP1A3 (tier 2)	(not checked)	1973	2016	-	White: British
7 (176)	Early onset and familial PD	homoz	PRKN (tier 2, hom missense, 6:161785820, hg38)	(not checked)	1964	2018	-	White: British
8 (410)	Ultra-rare undescribed monogenic disorders	unclear	PRKN (tier 2, hom missense, 6:161785820, hg38) CDK10 (tier 2)	G403, G409 (Epilepsy)	unclear	unclear	unclear	unclear
9 (044)	Hereditary ataxia	CH	PRKN (tier 2, het missense, 6:162271498, hg38) PRKN (tier 2, het missense, 6:162443419, hg38) SYNJ1, PLP1, SYNE1 (tier 2)	G113, G119 G249 (dystonia)	1969	2016	-	Black: Caribbean
10 (347)	Hereditary spastic paraplegia	HOMO	PRKN (tier 2, hom missense, 6:161973309, hg38) GRIN2D, IFIH1, REEP1, ARV1, USP9X (tier 2)	G801	2004	2018	-	Pakistani
11 (000)	Early onset and familial PD	CH	PRKN (tier 2, het missense, 6:161973317, hg38) PRKN (tier 2, het missense, 6:161350187, hg38)	(not checked)	1993	2018	-	White: British
12 (806)	Hereditary spastic paraplegia	Homoz	PITRM1 (tier 1) PRKN (tier 2, hom missense, 6:161785820, hg38)	G114, G821 G20 (PD)	1965	2018	-	White: British

GE/GMS Participant Sample Matrix

Patient id	Primary indications	Mutations (focusing on tier 1 and tier 2 mutations)	hospital records related to PD/NS	LiHep Plasma	RNA blood	Serum
1 (285)	Early onset and familial PD	see participant mutation table	(not checked)	-	-	-
2 (990) GMC	Early onset and familial PD	see participant mutation table	(not checked)	-	-	-
3 (137)	Early onset dystonia	see participant mutation table	G249 (dystonia) G20 (PD)	-	9	-
4 (583) GMC	Early onset and familial PD	see participant mutation table	(not checked)	-	9	-
5 (506)	Early onset and familial PD	see participant mutation table	(not checked)	-	-	-
6 (880)	Early onset and familial PD	see participant mutation table	(not checked)	-	-	-
7 (176)	Early onset and familial PD	see participant mutation table	(not checked)	-	-	-
8 (410)	Ultra-rare undescribed monogenic disorders	see participant mutation table	G403, G409 (Epilepsy)	3	9	2
9 (044)	Hereditary ataxia	see participant mutation table	G113, G119 G249 (dystonia)	-	-	-
10 (347)	Hereditary spastic paraplegia	see participant mutation table	G801	-	-	-
11 (000)	Early onset and familial PD	see participant mutation table	(not checked)	-	-	-
12 (806)	Hereditary spastic paraplegia	see participant mutation table	G114, G821 G20 (PD)	-	-	-

Sample Collection Requirements

Sample Type	Purpose	Collection Strategy	Required tubes	Blood volumes
RNA-stabilised blood	Transcriptomics	Expected where reasonable for probands & affected relatives. Optional for all unaffected relatives.	PAXgene® blood RNA	2.5ml
Plasma collected for ctDNA	ctDNA	Optional for all cancer patients at diagnosis; 2-6 weeks post-surgery; at regular intervals post treatment and/ or at recurrence.	Streck® or alternative	1-12 x 5mls
Blood for plasma	Metabolomics	Optional for all probands & affected relatives. Not required for unaffected relatives.	PST	8ml
Blood for serum	Proteomics	Optional for all probands & affected relatives. Not required for unaffected relatives.	SST	8.5ml

MP-PD Parkin Variant Reanalysis

MP-PD
 
- 197 PRKN LoF + Deleterious missense carriers
  - 이중 84 가 PD patients (여기 prodromal not included)
  - 2 Homozygous, 1 compound hetero, 80 single hetero, ): big impact!
 
Reanalysis 20210703
 
- IN PD (1272 중) 20 개의 ('potentially) pathogenic variant 존재,
  근데 이게 clinvar, helix (deleterious missense), VEP HC
  (protein truncation variants) 다 혼합한 것이며 결국 아래 기존의 list 와 동일하네!.
- IN PD (1272 중) 6.4% (81) heteroz, 0.15% (2) homoz
  (js: this is 43x)
- Among 57 prodromal PD cases, there were NO homo and 5 single hetero
  and 1 compound hetero (interesting that it is quite a lot compare to the PD group).
 
Questions
- Meaning of deleterious miss, splice donor variant
- Annotation and consequence term source? (since different from dbSNP)

Additional visible question fragment:

Meaning of deleterious missense
pathogenic on Helix?

Variant Annotation Comparison Table (top fragment)

		Jonghun slide	VEP	dbSNP		dbSNP		ClinVar	20210703
		consequence_term		Functional Consequence		Clinical significance:
no								Conflicting interpretations of …	Hetero PD 7명, homo PD 1명 vs …

Uncertain Spans

location	text/status	reason
participant table row 8	8 (410), Ultra-rare undescribed monogenic disorders, PRKN ... 6:161785820, CDK10 (tier 2), G403, G409 (Epilepsy)	Row is visible through a pale overlay/scroll transition and some year/ethnicity cells are not reliably readable.
lower comparison table	headers and first visible row only	Table continues beyond the bottom of the visible screen and is connected via related_photos to the following photo.