- Library Home /
- Search Collections /
- Open Collections /
- Browse Collections /
- UBC Faculty Research and Publications /
- Hunting for Familial Parkinson’s Disease Mutations...
Open Collections
UBC Faculty Research and Publications
Hunting for Familial Parkinson’s Disease Mutations in the Post Genome Era Bentley, Steven R.; Guella, Ilaria; Sherman, Holly E.; Neuendorf, Hannah M.; Sykes, Alex M.; Fowdar, Javed Y.; Silburn, Peter A.; Wood, Stephen A.; Farrer, Matthew J.; Mellick, George D.
Abstract
Parkinson’s disease (PD) is typically sporadic; however, multi-incident families provide a powerful platform to discover novel genetic forms of disease. Their identification supports deciphering molecular processes leading to disease and may inform of new therapeutic targets. The LRRK2 p.G2019S mutation causes PD in 42.5–68% of carriers by the age of 80 years. We hypothesise similarly intermediately penetrant mutations may present in multi-incident families with a generally strong family history of disease. We have analysed six multiplex families for missense variants using whole exome sequencing to find 32 rare heterozygous mutations shared amongst affected members. Included in these mutations was the KCNJ15 p.R28C variant, identified in five affected members of the same family, two elderly unaffected members of the same family, and two unrelated PD cases. Additionally, the SIPA1L1 p.R236Q variant was identified in three related affected members and an unrelated familial case. While the evidence presented here is not sufficient to assign causality to these rare variants, it does provide novel candidates for hypothesis testing in other modestly sized families with a strong family history. Future analysis will include characterisation of functional consequences and assessment of carriers in other familial cases.
Item Metadata
| Title |
Hunting for Familial Parkinson’s Disease Mutations in the Post Genome Era
|
| Creator | |
| Contributor | |
| Publisher |
Multidisciplinary Digital Publishing Institute
|
| Date Issued |
2021-03-17
|
| Description |
Parkinson’s disease (PD) is typically sporadic; however, multi-incident families provide a powerful platform to discover novel genetic forms of disease. Their identification supports deciphering molecular processes leading to disease and may inform of new therapeutic targets. The LRRK2 p.G2019S mutation causes PD in 42.5–68% of carriers by the age of 80 years. We hypothesise similarly intermediately penetrant mutations may present in multi-incident families with a generally strong family history of disease. We have analysed six multiplex families for missense variants using whole exome sequencing to find 32 rare heterozygous mutations shared amongst affected members. Included in these mutations was the KCNJ15 p.R28C variant, identified in five affected members of the same family, two elderly unaffected members of the same family, and two unrelated PD cases. Additionally, the SIPA1L1 p.R236Q variant was identified in three related affected members and an unrelated familial case. While the evidence presented here is not sufficient to assign causality to these rare variants, it does provide novel candidates for hypothesis testing in other modestly sized families with a strong family history. Future analysis will include characterisation of functional consequences and assessment of carriers in other familial cases.
|
| Subject | |
| Genre | |
| Type | |
| Language |
eng
|
| Date Available |
2021-03-26
|
| Provider |
Vancouver : University of British Columbia Library
|
| Rights |
CC BY 4.0
|
| DOI |
10.14288/1.0396400
|
| URI | |
| Affiliation | |
| Citation |
Genes 12 (3): 430 (2021)
|
| Publisher DOI |
10.3390/genes12030430
|
| Peer Review Status |
Reviewed
|
| Scholarly Level |
Faculty
|
| Rights URI | |
| Aggregated Source Repository |
DSpace
|
Item Media
Item Citations and Data
Rights
CC BY 4.0