Activity

Filter

Cancel
Date Panel Item Activity
15 actions
Parkinson Disease and Complex Parkinsonism v1.128 ARSA Ida Ertmanska commented on gene: ARSA: Comment on list classification: ARSA deficiency is a well-established cause of recessive metachromatic leukodystrophy. There is also some emerging evidence that heterozygous variants in ARSA may be a genetic modifier of Parkinson's disease. However, heterozygous variants act as risk factors, rather than causing familial dominant disease. Hence, the mode of inheritance should remain as 'BIALLELIC, autosomal or pseudoautosomal' on this panel.
Parkinson Disease and Complex Parkinsonism v1.128 ARSA Ida Ertmanska edited their review of gene: ARSA: Changed phenotypes to: Metachromatic leukodystrophy, OMIM:250100, metachromatic leukodystrophy, MONDO:0018868, arylsulfatase A deficiency
Parkinson Disease and Complex Parkinsonism v1.128 ARSA Ida Ertmanska edited their review of gene: ARSA: Changed phenotypes to: Metachromatic leukodystrophy, OMIM:250100
Parkinson Disease and Complex Parkinsonism v1.128 ARSA Ida Ertmanska changed review comment from: PMID: 37381728 Senkevich et al., 2023
Authors performed burden analyses in six independent cohorts with 5801 PD patients and 20,475 controls, followed by meta-analysis, and found evidence for associations between rare functional ARSA variants and PD in four cohorts (P ≤ 0.05 in each). Of note: "results should be interpreted with caution as no association survived multiple comparisons correction."

Authors also found potential co-segregation of p.E382K variant in two unrelated PD patients with history of MLD and PD. The variant was not found in any controls.
Family A, patient II-4 - 62yo, had Parkinson's disease, het for p.E382K; also a carrier of the GBA1 variant RecNcil - hence, impossible to estimate the role of the ARSA variant in PD.
Family A, individual IV-1 - 12yo, diagnosed with MLD, comp het for ARSA variants p.E382K and c.465G>T, p.Q155H.
Caveat: variant p.E382K = c.1150G>A, p.Glu384Lys (p.E384K) - MAF = 0.00005331 in gnomAD v4.1.1., no homozygotes. P/LP classification in ClinVar.
Family B: 5 family members with Parkinson's disease, 4 deceased and not genotyped (77-82yrs), individual II-4 (72yo) had PD and was ARSA wt/wt. Individual IV-1: 7yo, MLD diagnosis, comp het for ARSA variants p.E382K and c.1107+1G>A. Other het p.E382K carriers are aged under 60yo so not known if they will be affected by PD.

p.L300V variant found in two cases and one controls

PMID: 31312839 Lee et al., 2019
"ARSA is a genetic modifier of Parkinson's disease pathogenesis, acting as a molecular chaperone for α-synuclein."; to: PMID: 37381728 Senkevich et al., 2023
Authors performed burden analyses in six independent cohorts with 5801 PD patients and 20,475 controls, followed by meta-analysis, and found evidence for associations between rare functional ARSA variants and PD in four cohorts (P ≤ 0.05 in each). Of note: "results should be interpreted with caution as no association survived multiple comparisons correction."

Authors also found potential co-segregation of p.E382K variant in two unrelated PD patients with history of MLD and PD. The variant was not found in any controls.
Family A, patient II-4 - 62yo, had Parkinson's disease, het for p.E382K; also a carrier of the GBA1 variant RecNcil - hence, impossible to estimate the role of the ARSA variant in PD.
Family A, individual IV-1 - 12yo, diagnosed with MLD, comp het for ARSA variants p.E382K and c.465G>T, p.Q155H.
Caveat: variant p.E382K = c.1150G>A, p.Glu384Lys (p.E384K) - MAF = 0.00005331 in gnomAD v4.1.1., no homozygotes. P/LP classification in ClinVar.
Family B: 5 family members with Parkinson's disease, 4 deceased and not genotyped (77-82yrs), individual II-4 (72yo) had PD and was ARSA wt/wt. Individual IV-1: 7yo, MLD diagnosis, comp het for ARSA variants p.E382K and c.1107+1G>A. Other het p.E382K carriers are aged under 60yo so not known if they will be affected by PD.

PMID: 31312839 Lee et al., 2019
Reported a 32yo female proband with MLD, comp het for ARSA variants p.L300S and p.C174Y. Her father and paternal uncle had Parkinson's disease, and were heterozygous for the ARSA p.L300S variant - thought to be a potential risk factor.
Also analysed 92 cases with familial dominant Parkinson's disease. ARSA p.N352S was found to be a protective variant (more common in controls than PD cohort).
"ARSA is a genetic modifier of Parkinson's disease pathogenesis, acting as a molecular chaperone for α-synuclein." In cell lines, authors showed that ARSA deficiency correlates with an increase in α-synuclein aggregation.
Parkinson Disease and Complex Parkinsonism v1.128 ARSA Ida Ertmanska changed review comment from: PMID: 37381728 Senkevich et al., 2023
Authors performed burden analyses in six independent cohorts with 5801 PD patients and 20,475 controls, followed by meta-analysis, and found evidence for associations between rare functional ARSA variants and PD in four cohorts (P ≤ 0.05 in each). Of note: "results should be interpreted with caution as no association survived multiple comparisons correction."

p.L300V variant found in two cases and one control

Also found potential co-segregation of p.E382K variant in two unrelated PD patients with history of MLD and PD. However, one of the patients, II-4 from the first family, was also a carrier of the GBA1 variant RecNcil - which impossible to estimate the role of the ARSA variant in PD. The variant was not found in any controls.
Caveat: the variant is referred to as p.E382K and p.E384K in different parts of the publication. Likely to be the c.1150G>A, p.Glu384Lys variant - MAF = 0.00005331 in gnomAD v4.1.1., no homozygotes. P/LP classification in ClinVar.

PMID: 31312839 Lee et al., 2019
"ARSA is a genetic modifier of Parkinson's disease pathogenesis, acting as a molecular chaperone for α-synuclein."; to: PMID: 37381728 Senkevich et al., 2023
Authors performed burden analyses in six independent cohorts with 5801 PD patients and 20,475 controls, followed by meta-analysis, and found evidence for associations between rare functional ARSA variants and PD in four cohorts (P ≤ 0.05 in each). Of note: "results should be interpreted with caution as no association survived multiple comparisons correction."

Authors also found potential co-segregation of p.E382K variant in two unrelated PD patients with history of MLD and PD. The variant was not found in any controls.
Family A, patient II-4 - 62yo, had Parkinson's disease, het for p.E382K; also a carrier of the GBA1 variant RecNcil - hence, impossible to estimate the role of the ARSA variant in PD.
Family A, individual IV-1 - 12yo, diagnosed with MLD, comp het for ARSA variants p.E382K and c.465G>T, p.Q155H.
Caveat: variant p.E382K = c.1150G>A, p.Glu384Lys (p.E384K) - MAF = 0.00005331 in gnomAD v4.1.1., no homozygotes. P/LP classification in ClinVar.
Family B: 5 family members with Parkinson's disease, 4 deceased and not genotyped (77-82yrs), individual II-4 (72yo) had PD and was ARSA wt/wt. Individual IV-1: 7yo, MLD diagnosis, comp het for ARSA variants p.E382K and c.1107+1G>A. Other het p.E382K carriers are aged under 60yo so not known if they will be affected by PD.

p.L300V variant found in two cases and one controls

PMID: 31312839 Lee et al., 2019
"ARSA is a genetic modifier of Parkinson's disease pathogenesis, acting as a molecular chaperone for α-synuclein."
Parkinson Disease and Complex Parkinsonism v1.128 ARSA Ida Ertmanska changed review comment from: PMID: 37381728 Senkevich et al., 2023
Authors performed burden analyses in six independent cohorts with 5801 PD patients and 20,475 controls, followed by meta-analysis, and found evidence for associations between rare functional ARSA variants and PD in four cohorts (P ≤ 0.05 in each). Of note: "results should be interpreted with caution as no association survived multiple comparisons correction."

PMID: 31312839 Lee et al., 2019
"ARSA is a genetic modifier of Parkinson's disease pathogenesis, acting as a molecular chaperone for α-synuclein."; to: PMID: 37381728 Senkevich et al., 2023
Authors performed burden analyses in six independent cohorts with 5801 PD patients and 20,475 controls, followed by meta-analysis, and found evidence for associations between rare functional ARSA variants and PD in four cohorts (P ≤ 0.05 in each). Of note: "results should be interpreted with caution as no association survived multiple comparisons correction."

p.L300V variant found in two cases and one control

Also found potential co-segregation of p.E382K variant in two unrelated PD patients with history of MLD and PD. However, one of the patients, II-4 from the first family, was also a carrier of the GBA1 variant RecNcil - which impossible to estimate the role of the ARSA variant in PD. The variant was not found in any controls.
Caveat: the variant is referred to as p.E382K and p.E384K in different parts of the publication. Likely to be the c.1150G>A, p.Glu384Lys variant - MAF = 0.00005331 in gnomAD v4.1.1., no homozygotes. P/LP classification in ClinVar.

PMID: 31312839 Lee et al., 2019
"ARSA is a genetic modifier of Parkinson's disease pathogenesis, acting as a molecular chaperone for α-synuclein."
Parkinson Disease and Complex Parkinsonism v1.128 ARSA Ida Ertmanska reviewed gene: ARSA: Rating: AMBER; Mode of pathogenicity: None; Publications: 31312839, 37381728; Phenotypes: Menkes disease, OMIM:309400, Neuronopathy, distal hereditary motor, X-linked, OMIM:300489; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Parkinson Disease and Complex Parkinsonism v1.126 ARSA Sarah Leigh Publications for gene: ARSA were set to 37381728; 31312839
Parkinson Disease and Complex Parkinsonism v1.125 ARSA Sarah Leigh Phenotypes for gene: ARSA were changed from to Metachromatic leukodystrophy, OMIM:250100; metachromatic leukodystrophy, juvenile form, MONDO:0009591
Parkinson Disease and Complex Parkinsonism v1.124 ARSA Sarah Leigh Classified gene: ARSA as Amber List (moderate evidence)
Parkinson Disease and Complex Parkinsonism v1.124 ARSA Sarah Leigh Gene: arsa has been classified as Amber List (Moderate Evidence).
Parkinson Disease and Complex Parkinsonism v1.123 ARSA Sarah Leigh Publications for gene: ARSA were set to PMID: 37381728 PMID: 31312839 PMID: 31312839
Parkinson Disease and Complex Parkinsonism v1.122 ARSA Sarah Leigh Classified gene: ARSA as Green List (high evidence)
Parkinson Disease and Complex Parkinsonism v1.122 ARSA Sarah Leigh Gene: arsa has been classified as Green List (High Evidence).
Parkinson Disease and Complex Parkinsonism v1.121 ARSA David Collier gene: ARSA was added
gene: ARSA was added to Parkinson Disease and Complex Parkinsonism. Sources: Expert list
Mode of inheritance for gene: ARSA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARSA were set to PMID: 37381728 PMID: 31312839 PMID: 31312839
Penetrance for gene: ARSA were set to unknown
Review for gene: ARSA was set to AMBER
Added comment: Association bertween these gene and Parkinson's has been controversial, however a recent publication adds to the supportive evidence for this gene (PMID: 37381728). Gene for Metachromatic leukodystrophy (MIM 250100 AR)
Sources: Expert list