Mitochondrial dysfunction and autism: comprehensive genetic analyses of children with autism and mtDNA deletion

Table 3 Results of the intergenomic NGS panel

Patient ID	Gene	Mutation	Zygosity	Inheritance	Clinical relevance	Polyphen2	SIFT	MT	dbSNP	ExAC	1000 Genomes/EUR AF
Patients with ASD and mtDNA deletion (N = 10)
P5	MGME1	T265I	HET	AR	Likely pathogenic [37]	0.95	0.25	D	rs76599088	0.007875	0.0044/0.0139
P9	SUCLG1	G79D	HET	AR	Uncertain significance	0.99	0	D	n/d	n/d	n/d
Patients with ASD and without mtDNA deletion (N = 7)
C-ASD1	MTO1	K321E	HET	AR	Uncertain significance	1	0.001	D	rs148667065	0.0000908	n/d
C-ASD2	EARS2	R99Q	HET	AR	Uncertain significance	n/d	1	D	n/d	n/d	n/d
Patients with MD and mtDNA deletion, without ASD (N = 7)
C-MD1	WARS2	H151R	HET	AD/AR	Uncertain significance	0.1	0.02	D	rs150022801	0.001779	0.0008/0.003
C-MD2	APEX1	R202P	HET	n/d	Uncertain significance	0.6	0.01	P	n/d	0.000008242	n/d
C-MD3	ATP5A1	I173 V	HET	AR	Uncertain significance	0.02	0.1	D	n/d	n/d	n/d
C-MD4	MTO1	V517 M	HET	AR	Uncertain significance	0.03	0.1	D	n/d	n/d	n/d
C-MD5	C10orf2	N399S	HET	AR	Pathogenic [38]	0.896	0.09	D	n/d	n/d	n/d
C-MD5	C10orf2	A453Q	HET	AR	Uncertain significance	0.053	0.27	D	n/d	n/d	n/d
C-MD6	MRPL3	S75 N	HET	AR	Pathogenic [56]	0.8	0.34	D	rs151331067	0.001606	0.0008/n/d
Healthy controls without mtDNA deletion (N = 6)
C-H3	EARS2	S482 N	HET	AR	Uncertain significance	n/d	0.28	D	n/d	n/d	n/d
C-H4	SLC25A3	V219F	HET	AD	Uncertain significance	0.62	0.001	D	n/d	n/d	n/d

Pathogenic, likely pathogenic, and rare variants of uncertain significance detected in the 10 mtdel-ASD cases and different comparison groups are presented (benign variations are not shown)
P mtdel-ASD patient, non-mtdel-ASD ASD patient without mtDNA deletion, MD patient with mitochondrial disease, H healthy control individual, HET heterozygous, AR autosomal recessive, AD autosomal dominant, n/d no data, SIFT sorting intolerant from tolerant prediction database, MT mutation t@ster prediction database, D disease causing according to mutation t@ster prediction, P polymorphism according to mutation t@ster prediction, ExAC allele frequency data from exome aggregation consortium, 1000 Genomes allele frequency data from 1000 Genomes project, EUR AF allele frequency in the European Super Population of the 1000 Genomes project

ISSN: 1744-9081