New perspective in diagnostics of mitochondrial disorders: two years’ experience with whole-exome sequencing at a national paediatric centre

Pronicka, Ewa; Piekutowska-Abramczuk, Dorota; Ciara, Elżbieta; Trubicka, Joanna; Rokicki, Dariusz; Karkucińska-Więckowska, Agnieszka; Pajdowska, Magdalena; Jurkiewicz, Elżbieta; Halat, Paulina; Kosińska, Joanna; Pollak, Agnieszka; Rydzanicz, Małgorzata; Stawinski, Piotr; Pronicki, Maciej; Krajewska-Walasek, Małgorzata; Płoski, Rafał

doi:10.1186/s12967-016-0930-9

Table 2 Molecular variants identified in 67 individuals of the study group

From: New perspective in diagnostics of mitochondrial disorders: two years’ experience with whole-exome sequencing at a national paediatric centre

Gene	Chromosome:RefSeq	Variant 1			Variant 2			Zygosity status	Mode	ID patient
Gene	Chromosome:RefSeq	Type	Status	Origin	Type	Status	Origin	Zygosity status	Mode	ID patient
Mitochondrial disease gene
ACAD9	chr3:NM_014049.4	c.514G>A/p.Gly172Arg	Novel	mat	c.803C>T/p.Ser268Phe	Novel	pat	comphtz	AR	15
ACAD9	chr3:NM_014049.4	c.1552C>T/p.Arg518Cys	Known	mat	c.1553G>A/p.Arg518His	Known	pat	comphtz	AR	23
ACAD9	chr3:NM_014049.4	c.728C>G/p.Thr243Arg	Novel	ND	c.1552C>T/p.Arg518Cys	Known	mat	comphtz	AR	53
ADCK3	chr1:NM_020247.4	c.827A>G/p.Lys276Arg	Novel	mat	c.1702delG/p.Gly568Argfs	Novel	pat	comp htz	AR	61
AIFM1	chrX:NM_004208.3	c.1474T>C/p.Tyr492His	Novel	mat	–		–	hemi	XLR	25
CLPB	chr11:NM_030813.4	c.2045T>A/p.Ile682Asn	Known	pat	c.1937_1938insG/p.645Gly_646Cysfs	Known	mat	comphtz	AR	5
CLPB	chr11:NM_030813.4	c.1249C>T/p.Arg417^a	Known	pat	c.748C>T/p.Arg250^a	Known	mat	comphtz	AR	27
CLPB	chr11:NM_030813.4	c.1249C>T/p.Arg417^a	Known	pat	c.1222A>G/p.Arg408Gly	Known	mat	comphtz	AR	67
COX10	chr17:NM_001303.3	c.1030A>G/p.Met344Val	Novel	pat	c.1270dupC/p.Leu424Profs	Novel	mat	comphtz	AR	9
COX10	chr17:NM_001303	c.674C>T/p.Pro225Leu	Known	mat	c.674C>T/p.Pro225Leu	Known	pat	hom	AR	36
DLD	chr7:NM_000108.4	c.1123G>A/p.Glu375Lys	Known	mat	c.1123G>A/p.Glu375Lys	Known	pat	hom	AR	31
EARS2	chr16:NM_001083614.1	c.164G>A/p.Arg55His	Known	mat	c.325G>C/p.Gly109Arg	Novel	pat	comphtz	AR	7
EARS2	chr16:NM_001083614.1	c.164G>A/p.Arg55His	Known	pat	c.1256C>T/p.Pro419Leu	Novel	mat	comphtz	AR	70
FBXL4	chr6:NM_012160.4	c.858+1G>T/p.?	Novel	pat	c.585+5G>C/p.?	Novel	mat	comphtz	AR	3
FBXL4	chr6:NM_012160.4	c.1303C>T/p.Arg435^a	Known	ND	c.64C>T/p.Arg22^a	Novel	mat	comphtz	AR	52
FBXL4	chr6:NM_012160.4	c.64C>T/p.Arg22^a	Novel	mat	c.64C>T/p.Arg22^a	Novel	pat	hom	AR	55
MTATP6	chrM:NC_012920.1	m.9185T>C/p.Leo220Pro	Known	mat	–		–	hompl	M	32
MTFMT	chr15:NM_139242.3	c.994C>T/p.Arg332^a	Known	ND	c.626C>T/p.Ser209Leu	Known	ND	comphtz	AR	91
MTND1	chrM:NC_012920.1	m.3902_3908invACCTTGC/p.?	Known	de novo	–		–	hetpl	M	22
MTND1	chrM:NC_012920.1	m.3688G>A/p.Ala128Thr	Known	ND	–		–	hompl	M	64
MTND3	chrM:NC_012920.1	m.10254G>A/p.Asp66Asn	Known	de novo	–		–	hetpl	M	57
MTND5	chrM:NC_012920.1	m.12706T>C/p.Phe124Leu	Known	de novo	–		–	hetpl	M	34
MTND5	chrM:NC_012920.1	m.13513G>A/p.Asp393Asn	Known	de novo	–		–	hetpl	M	35
NAXE	chr1:NM_144772.2	c.653A>T/p.Asp218Val	Known	mat	c.743_744delC/p.247Ala_248Thrfs	Known	pat	comphtz	AR	12
NDUFS6	chr5:NM_004553.4	c.313_315delAAAG/p.104Lys_106Thrfs	Novel	pat	c.334_359del26ins13/p.Glu112 fs	Novel	mat	comphtz	AR	1
NDUFS7	chr19:NM_024407.4	c.376C>T/p.Leu126Phe	Novel	ND	c.504G>C/p.Arg168Ser	Novel	ND	het	AR	75
NDUFV1	chr11:NM_007103.3	c.733G>A/p.Val245Met	Novel	pat	c.383G>T/p.Arg128Leu	Novel	mat	comphtz	AR	10
OPA1	chr3:NM_015560.2	c.1146A>G/p.Ile382Met	Known	mat	–		–	htz	AD	33
PARS2	chr1:NM_152268.3	c.1091C>G/p.Pro364Arg	Novel	mat	c.239T>C/p.Ile80Thr	Novel	pat	comphtz	AR	60
PC	chr11:NM_000920.3	c.808C>T/p.Arg270Trp	Known	pat	c.2381_2383delTGG/p.Val794del	Novel	mat	comphtz	AR	29
PC	chr11:NM_000920.3	c.1487G>A/p.Arg496Gln	Novel	ND	c.584C>T/p.Ala195Val	Novel	ND	comphtz	AR	71
PDHA1	chr X:NM_000284.3	c.262C>T/p.Arg88Cys	Known	mat	–		–	hemi	XLD	19
PDHA1	chrX:NM_000284.3	c.856_859dupACTT/p. Arg288Leufs	Novel	de novo	–		–	htz	XLD	56
PDHA1	chrX:NM_000284.3	c.933_935del/p.Arg311del l	Known	de novo	–		–	htz	XLD	66
PDHA1	chrX:NM_000284.3	c.291G>A/p.?	Novel	de novo	–		–	hemi, mosaic	XLD	68
POLG	chr15:NM_001126131.1	c.2639C>A/p.Ala880Asp	Novel	pat	c.2243G>C/p.Trp748Ser	Known	mat	comphtz	AR	113
RARS2	chr6:NM_020320.3	c.1026G>A/p.Met342Ile	Novel	mat	c.622C>T/p.Gln208^a	Novel	pat	comphtz	AR	41
RRM2B	chr8:NM_015713.4	c.414_415delCA/p.Tyr138^a	Novel	mat	c.414_415delCA/p.Tyr138^a	Novel	ND	hom	AR	21
RRM2B	chr8:NM_015713.4	c.686G>T/p.Gly229Val	Known	mat	c.686G>T/p.Gly229Val	Known	pat	hom	AR	51
SCO2	chr22:NM_005138.2	c.418G>A/p.Glu140Lys	Known	ND	c.418G>A/p.Glu140Lys	Known	ND	hom	AR	54
SERAC1	chr6:NM_032861.3	c.1822_1828+10delinsACCAACAGG	Known	ND	c.1822_1828+10delinsACCAACAGG	Known	ND	hom	AR	37
SLC19A3	chr2:NM_025243.3	c.68G>T/p.Gly23Val	Known	Pending	c.68G>T/p.Gly23Val	Known	Pending	hom	AR	58
SLC19A3	chr2:NM_025243.3	c.74dupT/p.Ser26Leufs	Known	ND	c.74dupT/p.Ser26Leufs	Known	ND	hom	AR	109
SLC25A12	chr2:NM_003705.4	c.1335C>A/p.Asn445Lys	Novel	mat	c.1335C>A/p.Asn445Lys	Novel	pat	hom	AR	24
TAZ	chrX:NM_000116.3	c.684_685insC/p.227Phe_228Profs	Novel	ND	–		–	hemi	XLR	28
TMEM126B ^a	chr11:NM_018480.4	c.635G>T/p.Gly212Val	Known	mat	c.635G>T/p.Gly212Val	Known	pat	hom	AR	59
VARS2	chr6:NM_001167734.1.5	c.1100C>T/p.Thr367Ile	Known	Pending	c.1490G>A/p.Arg497His	Novel	Pending	comphtz	AR	97
Non mitochondrial disease gene
ADAR	chr1:NM_001111.4	c.3202+1G>A/p.?	Novel	ND	c.577C>G/p.Pro193Ala	Known	ND	comphtz	AR	18
CACNA1A	chr19:NM_001127221.1	c.1997C>T/p.Thr666Met	Known	mat	–		–	htz	AD	39
CDKL5	chrX:NM_003159.2	c.1942C>T/p.Gln648^a	Novel	mat	–		–	hemi	XLD	65
CLN3	chr16:NM_001042432.1	c.954_962+18del27/p.Leu313_Trp321del	Known	pat	c.461-280_677+382del966	Known	Pending	comphtz	AR	88
CPS1	chr2:NM_001875.4	c.1837-8A>G/p.?	Known	mat	c.3691G>C/p.Ala1231Pro	Novel	Paternal	comphtz	AR	13
CPS1	chr2:NM_001875.4	c.1289C>G/p.Ser430^a	Novel	mat	c.3971_3972delT/p.1323Ile_1324Leufs	Novel	pat	comphtz	AR	40
DMD	chr X:NM_004006	c.31+1G>A/p.?	Novel	mat	–		–	hemi	XLR	38
DYSF	chr2:NM_003494.3	c.1180+5G>A/p.?	Known	ND	c.6124C>T/p.Arg2042Cys	Known	ND	comphtz	AR	45
GBE1	chr3:NM_000158.3	c.1621A>T/p.Asn541Tyr	Novel	mat	c.263G>A/p.Cys88Tyr	Novel	pat	comphtz	AR	14
GFAP	chr17:NM_002055.4	c.1100G>C/p.Arg367Thr	Novel	de novo	–		–	htz	AD	42
HSD17B4	chr5:NM_000414.3	c.46G>A/p.Gly16Ser	Known	ND	c.367C>T/p.His123Tyr	Novel	ND	comphtz	AR	30
MECP2	chrX:NM_004992.3	c.89delA/p.Lys30Argfs	Novel	de novo	–		–	hemi	XLD	106
MYBPC3	chr11:NM_000256.3	c.1351+1G>A/p.?	Known	pat	–		–	htz	AD	8
PEX5	chr12:NM_001131025.1	c.1669C>T/p.Arg557Trp	Known	mat	c.1799C>T/p.Ser600Leu	Novel	pat	comphtz	AR	20
PGAP2	chr11:NM_001256240.1	c.2T>G/p.Met1?	Known	mat	c.221G>A/p.Arg74His	Known	pat	comphtz	AR	73
PIGN	chr18:NM_176787.4	c.932T>G/p.Leu311Trp	Known	mat	c.790G>A/p.Gly264Arg	Known	pat	comphtz	AR	6
PRF1	chr10:NM_001083116.1	c.808_812delGGCAG/p.Gly270 fs	Novel	mat	c.658G>A/p.Gly220Ser	Known	pat	comphtz	AR	2
SBDS	chr7:NM_016038.2	c.258+2T>C/p.?	Known	pat	c.184A>T/p.Lys62^a	Novel	mat	comphtz	AR	95
SCN2A	chr2:NM_021007.2	c.2948T>G/p.Leu983Trp	Novel	de novo	–		–	htz	AD	47
New candidate gene for mitochondrial disease
NDUFB8	chr10:NM_005004.3	c.432C>G/p.Cys144Trp	Novel	mat	c.227C>A/p.Pro76Gln	Novel	pat	comphtz	AR	26

mat maternal, pat paternal, ND not determined (DNA not available), hom homozygote, htz heterozygote, comp htz compound heterozygote, hemi hemizygote, hompl homoplasmic, hetpl heteroplasmic, AR autosomal recessive inheritance, AD autosomal dominant inheritance, XLR X-linked recessive inheritance, XLD X-linked dominant inheritance, M mitochondrial inheritance
^aData published on ESHG 2016 by Alston et al.

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