Additional file 1 of Contribution of rare homozygous and compound heterozygous VPS13C missense mutations to dementia with Lewy bodies and Parkinson’s disease
Creators: name: Smolders, Stefanie
name: Philtjens, Stéphanie
name: Crosiers, David
name: Sieben, Anne
name: Hens, Elisabeth
name: Bavo Heeman
name: Mossevelde, Sara Van
name: Pals, Philippe
name: Asselbergh, Bob
name: Dias, Roberto Dos Santos
name: Vermeiren, Yannick
name: Vandenberghe, Rik
name: Engelborghs, Sebastiaan
name: Deyn, Peter Paul De
name: Jean-Jacques Martin
name: Cras, Patrick
name: Annaert, Wim
name: Broeckhoven, Christine Van
Publisher: name: figshare
Year: 2021
Subjects: subject: Biophysics
subject: 29999 Physical Sciences not elsewhere classified
subject: FOS: Physical sciences
subject: FOS: Physical sciences
subject: Genetics
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Neuroscience
subject: Physiology
subject: Pharmacology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: FOS: Chemical sciences
subject: Cancer

description: Additional file 1. Supplementary materials and methods. Detailed protocols and references. Supplementary results. Phasing compound heterozygous variants in the Belgian cohorts. Effect of VPS13C splice site variants on mRNA splicing. Supplementary tables. Table S1: Clinical and demographic characteristics of study cohorts. Table S2. Clinical data of patient carriers of rare homozygous or trans compound heterozygous VPS13C mutations. Table S3: Candidate genes and mutations identified in WGS data of family A. Table S4: VPS13C rare coding and splice site variants in DLB and PD patients and in controls. Table S5: Major genes associated with neurodegenerative brain diseases. Table S6: LBD patient carriers of cis compound heterozygous coding and splice site variants in VPS13C. Table S7: Control carriers of compound heterozygous coding and splice site variants in VPS13C. Table S8: Primer sequences. Table S9: In-silico predictions on VPS13C mRNA splicing of splice site variants in compound heterozygous carriers. Supplementary figures. Fig. S1: VPS13C rare coding and splice site variants in DLB (n=233) and PD patients (n=611), and in controls (844). Fig. S2: Late endosomal localization of VPS13C is lost in p.Trp395Cys and p.Ala444Pro mutations. Fig. S3: Lysosomal localization of VPS13C is lost in p.Trp395Cys and p.Ala444Pro mutations. Fig. S4: Missense mutations p.Trp395Cys and p.Ala444Pro disturb localization of VPS13C at the lysosomes. Fig. S5: Wild type and p.Trp395Cys or p.Ala444Pro mutant VPS13C does not accumulate at the endoplasmic reticulum. Fig. S6: Wild type and p.Trp395Cys or p.Ala444Pro mutant VPS13C does not accumulate at the cis- and medial-Golgi. Fig. S7: Wild type and p.Trp395Cys or p.Ala444Pro mutant VPS13C does not accumulate at the trans-Golgi. Fig S8: Western blot analysis of extracts from VPS13C knockout and wild type HeLa cells using the affinity-purified VPS13C antibody. Fig. S9: Haplotype sharing analysis. Fig. S10: Trans configuration of p.Met2711Ile/p.Ile2789Thr in patient P4 confirmed by allele specific PCR. Fig. S11: Family C. Fig. S12: Cis configuration of p.Met2764Ile/p.Val2765Leu in control C6. Fig. S13: Effect of c.4166-8C&gt;A on VPS13C mRNA splicing.