Syndromes associated with mitochondrial DNA depletion

Table 1 Relative frequency of mutations associated with the different mitochondrial DNA depletion syndromes (MDS, source: HGMD Professional database: http://www.hgmd.cf.ac.uk/ )

Mitochondrial DNA depletion syndromes	Period of onset	Clinical features	Genes (aliases)	Chromosomal LOCI	Numbers of mutations	References*
Hepatocerebral mtDNA depletion syndrome	Neonatal, early childhood	Hepatic dysfunction; psychomotor delay; hypotonia; lactic acidosis; nystagmus; neurological dysfunction	POLG (Polg1/PolgA)	15q25	8	[10]
			C10orf2 (Twinkle/PEO1)	10q24	3	[11]
			DGUOK (dGK)	2p13	51	[12]
			MPV17 (SYM1)	2p23.3	28	[13]
			TK2	16q22-q23.1	1	[14]
Alpers-Huttenlocher syndrome	Early childhood	Hepatic dysfunction; epilepsia partialis continua; neurological dysfunction	POLG (Polg1/PolgA)	15q25	54	[15]
Myopathic mtDNA depletion syndrome	Infancy, early childhood	Hypotonia; muscle weakness; dysarthria and dysphagia; failure to thrive	POLG (Polg1/PolgA)	15q25	1	[5]
			TK2	16q22-q23.1	34	[16]
			RRM2B (p53R2)	8q23.1	3	[5]
			DGUOK (dGK)	2p13	1	[17]
Encephalomyopathic mtDNA depletion syndrome	Infancy	Hypotonia; muscle weakness; psychomotor delay; sensorineural hearing impairment; lactic acidosis; neurological dysfunction	RRM2B (p53R2)	8q23.1	14	[18]
			TK2	16q22-q23.1	1	[19]
			SUCLA2	13q12.2	9	[20]
			SUCLG1	2p11.3	13	[21]
Mitochondrial neurogastrointestinal encephalomyopathy	Late childhood, adolescence	Gastrointestinal dysmotility; weight loss; peripheral neuropathy;ptosis; neurological dysfunction	TYMP (ECGF1)	22q13	81	[22]
Mitochondrial neurogastrointestinal encephalomyopathy	Late childhood, adolescence		RRM2B (p53R2)	8q23.1	2	[23]
			POLG (Polg1/PolgA)	15q25	1	[24]

MDS are inherited in an autosomal recessive pattern; mutations in POLG gene outside MDS may be associated with autosomal recessive/dominant pattern of inheritance. *References of the first mutations published associated with the phenotype.

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