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dc.contributor.authorBentley, Steven R
dc.contributor.authorGuella, Ilaria
dc.contributor.authorSherman, Holly E
dc.contributor.authorNeuendorf, Hannah M
dc.contributor.authorSykes, Alex M
dc.contributor.authorFowdar, Javed Y
dc.contributor.authorSilburn, Peter A
dc.contributor.authorWood, Stephen A
dc.contributor.authorFarrer, Matthew J
dc.contributor.authorMellick, George D
dc.date.accessioned2021-11-02T01:50:19Z
dc.date.available2021-11-02T01:50:19Z
dc.date.issued2021
dc.identifier.issn2073-4425
dc.identifier.doi10.3390/genes12030430
dc.identifier.urihttp://hdl.handle.net/10072/409642
dc.description.abstractParkinson’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.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherMDPI
dc.relation.ispartofpagefrom430
dc.relation.ispartofissue3
dc.relation.ispartofjournalGenes
dc.relation.ispartofvolume12
dc.subject.fieldofresearchGenetics
dc.subject.fieldofresearchcode3105
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsGenetics & Heredity
dc.subject.keywordsfamilial
dc.subject.keywordsmulti-incident
dc.titleHunting for Familial Parkinson's Disease Mutations in the Post Genome Era
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationBentley, SR; Guella, I; Sherman, HE; Neuendorf, HM; Sykes, AM; Fowdar, JY; Silburn, PA; Wood, SA; Farrer, MJ; Mellick, GD, Hunting for Familial Parkinson's Disease Mutations in the Post Genome Era, GENES, 2021, 12 (3), pp. 430
dcterms.dateAccepted2021-03-13
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.date.updated2021-10-31T23:17:08Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorMellick, George
gro.griffith.authorSykes, Alex M.


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