Table 2.

Nuclear genes implicated in genetically solved mitochondrial disease cases presenting with dystonia

Functional category	Gene	Mode of inheritance	Neurological features other than dystonia	Extraneurological features	n. of cases
OXPHOS subunits, assembly factors, and electron carriers	ATP5F1E	AR	ID, ataxia, neuropathy		2
	ATP5PO	AR	DD, hypotonia, epilepsy, microcephaly		1
	BCS1L	AR	DD, hypotonia, ID, epilepsy, myoclonus, spasticity	Hypoglycemia, gastrointestinal dysmotility, lactic acidosis,	1
	COQ4	AR	DD, hypotonia, ID, epilepsy, microcephaly	Facial dysmorphism	3
	COX10	AR	DD, hypotonia, ataxia	Failure to thrive, lactic acidosis	1
	DNAJC30	AR	DD, ataxia		1
	FOXRED1	AR	DD, epilepsy, myoclonus, visual impairment	Lactic acidosis	1
	LYRM7	AR	DD/ DR, ID, hypotonia, microcephaly, deafness, visual impairment, tremor	Failure to thrive, hypoglycemia, facial dysmorphism, lactic acidosis, exercise intolerance	1
	NDUFA12	AR	DD/DR, ID, hypotonia, spasticity, visual impairment, microcephaly, tremor, neuropathy	Lactic acidosis, scoliosis	2
	NDUFA4	AR	DD/DR, ataxia	Failure to thrive, lactic acidosis, hypertrophic cardiomyopathy, myopathy, exercise intolerance	1
	NDUFAF5	AR	DD/DR, ataxia	Lactic acidosis	2
	NDUFAF6	AR	DD/DR, spasticity, ataxia, visual impairment	Gastrointestinal dysmotility, lactic acidosis, scoliosis	4
Mitochondrial DNA replication and expression	GFM1	AR	DD, epilepsy, spasticity, neuropathy, visual impairment	Muscular dystrophy, lactic acidosis	1
	GFM2	AR	DD/DR, hypotonia, ID, epilepsy, microcephaly, spasticity, neuropathy	Failure to thrive, gastrointestinal dysmotility, lactic acidosis, muscular dystrophy, exercise intolerance	1
	MRPS34	AR	DD, ID, microcephaly		1
	MTFMT	AR	DD, ID, hypotonia, ataxia, attention deficit-hyperactivity disorder	Failure to thrive, lactic acidosis, anemia, strabismus, hypertrophic cardiomyopathy	2
	PNPT1	AR	DR, ID		2
	SARS2	AR	DD/DR, hypotonia, spasticity	Lactic acidosis, cataract	1
	WARS2	AR	DD, ID, athetosis, hemiballismus,		1
Mitochondrial dynamics, homeostasis, and quality control	CLPB	AR	hypotonia, epilepsy	Neutropenia, anemia, apneas	1
	SERAC1	AR	DD, hypotonia, ID, spasticity, microcephaly, deafness, epilepsy, ataxia, optic atrophy	Failure to thrive, facial dysmorphism, lactic acidosis, hypoglycemia, kidney dysfunction, liver failure	3
	SPG7	AR	DD, ID, ataxia		1
	TIMM50	AR	DD, epilepsy, spasticity, optic atrophy	Failure to thrive, neutropenia, cardiomyopathy, lactic acidosis, scoliosis	1
	YME1L1	AR	DR, ataxia	Lactic acidosis, cardiomyopathy, exercise intolerance	1
Metabolism of substrates	ALDH18A1	AR	DD, hypotonia, ID, epilepsy, microcephaly, spasticity	Failure to thrive, cataract	1
	FA2H	AR	DD, ID, ataxia		2
	MDH2	AR	DD, epilepsy, hypotonia	Failure to thrive, lactic acidosis	1
	PDHA1	X-linked	DD, spasticity, visual impairment	Lactic acidosis	2
Metabolism of cofactors	COASY	AR	DD, ID, ataxia, spasticity		1
	FDXR	AR	hypotonia, ID, epilepsy, ataxia, spasticity, optic atrophy, visual impairment, deafness, ophthalmoplegia, neuropathy	Myopathy, diabetes mellitus	1
	ISCA2	AR	DD/DR, epilepsy, spasticity	Anemia, lactic acidosis	1
	LIPT2	AR	DD/DR, hypotonia, ID, microcephaly, epilepsy, spasticity	Lactic acidosis	2
	MECR	AR	DD		1
	PANK2	AR	DD, ID, ataxia, spasticity, tremor		3
	SEPSECS	AR	DD, ID		1
	SLC19A3	AR	DD, ataxia		2
	SLC25A42	AR	DD, hypotonia, ID, macrocephaly, choreoathetosis	Rhabdomyolysis, failure to thrive, gastrointestinal dysmotility, facial dysmorphism, lactic acidosis	2
	TPK1	AR	DD	Feeding difficulties, muscular dystrophy	1
Metabolism of toxic compounds	ECHS1	AR	DD/DR, ID, hypotonia, microcephaly, epilepsy, spasticity, ataxia, deafness, neuropathy, optic atrophy, stroke-like episodes,	Failure to thrive, gastrointestinal dysmotility, lactic acidosis, diabetes insipidus, abnormality of temperature regulation, hypertrophic cardiomyopathy, kidney dysfunction, exercise intolerance, hepatomegaly, apneas	16
	ETHE1	AR	DD/DR, myoclonus, ataxia, spasticity	Lactic acidosis	1
	HIBCH	AR	DD/DR	Failure to thrive	1
Others/Unknown function	C19orf12	AR	DD, ID, ataxia		2
	FBXL4	AR	DD, ID, hypotonia, spasticity		1
	PLA2G6	AR	DD, ID, ataxia		3
	SPATA5	AR	DD, epilepsy, microcephaly, myoclonus, spasticity, deafness, visual impairment	Failure to thrive, lactic acidosis	2

Genes associated with NBIAs are shown in bold. While some genes may be associated with both autosomal recessive (AR) and autosomal dominant inheritance (AD), we herein reported only the mode of inheritance specific to the variants detected in the present study. DD: developmental delay; DR: developmental regression; ID: intellectual disability