Contribution of rare homozygous and compound heterozygous VPS13C missense mutations to dementia with Lewy bodies and Parkinson’s disease

Table 1 LBD patients carrying rare homozygous or compound heterozygous mutations in VPS13C

Patient	Dx	AAO	∆CDS^a	ΔAA^b	MAF gnomAD_nfe (%)	CADD_Phred score^c	MAF patient cohort (%) n = 844	MAF control cohort (%) n = 664	Phase	F in patients (%)	F in controls (%)	F expected^d (%)
P1*^,$	DLB	42	c.1185G > C	p.Trp395Cys	–	33	0.0592	0	Trans	0.118	0	0.0000770
			c.1330G > C	p.Ala444Pro	0.00864	28.4	0.415	0
P2*	DLB	40	c.1330G > C	p.Ala444Pro	0.00864	28.4	0.415	0	Homozygous	0.118	0	0.0005
			c.1330G > C	p.Ala444Pro	0.00864	28.4	0.415	0
P3*^,$	DLB	58	c.3652A > G	p.Thr1218Ala	0.000781	26.4	0.0592	0	Trans	0.118	0	0.00020
			c.8366 T > C	p.Ile2789Thr	1.00	2.797	0.533	0.679
P4	DLB	84	c.8133G > A	p.Met2711Ile	0.00177	22.5	0.0592	0.0754	Trans	0.118	0	0.000396
			c.8366 T > C	p.Ile2789Thr	1.00	2.797	0.533	0.679
P5*	PD	60	c.5060C > T	p.Ala1687Val	0.314	22.5	0.0592	0.151	Trans	0.118	0	0.000264
			c.8711C > T	p.Ser2904Leu	0.343	26.7	0.178	0.378
P6*	DLB	42	c.2797A > G	p.Thr933Ala	0.577	12.67	0.711	0.452	Unknown	0.118	0	0.000991
			c.7276G > A	p.Val2426Ile	0.244	12.31	0.118	0.226
7*	PD	65	c.2296A > G	p.Thr766Ala	–	12.18	0.0592	0.0754	Unknown	0.118	0	0.0000220
			c.5537 T > C	p.Leu1846Ser	–	26.8	0.0592	0
P8	PD	73	c.4056 + 3A > C	–	0.00705	14.06	0.0592	0	Unknown	0.118	0	0.0000110
			c.7628C > G	p.Ser2543Cys	–	28.9	0.0592	0
P9	PD	73	c.8366 T > C	p.Ile2789Thr	1.00	2.797	0.533	0.679	Unknown	0.118	0	0.00337
			c.11176A > G	p.Ile3726Val	0.594	23.1	0.237	0.980

Clinical symptoms of LBD patients with (putative) recessive inherited mutations are summarized in Additional file 1: Table S2
Dx diagnosis, PD Parkinson’s disease, DLB Dementia with Lewy bodies, ∆CDS coding sequence substitution, ΔAA amino acid substitution, MAF minor allele frequency, F frequency of homozygotes and compound heterozygotes, AAO age at onset, gnomAD_nfe Genome Aggregation Database non-Finnish European population [23]
^*Lymphoblast cells available
^$brain tissue available
^aCoding nomenclature according to NM_020821
^bProtein nomenclature according to NP_0658721
^cCADD_Phred score [21]
^d Expected frequency is calculated according to the Hardy–Weinberg principle, using the MAF of the single alleles in patients plus controls (n = 1508)

ISSN: 2051-5960