Table 3.

Genes causally involved in the development of PRLTS and PRLTS-like features.

Gene (Locus)	Protein	Subcellular Localization	Function	Additional Clinical Features *	Inheritance Mode	Ref.
CLPP (19p13.3)	caseinolytic mitochondrial matrix peptidase proteolytic subunit	mitochondrial	mitochondrial protein degradation (component of a proteolytic complex)	•neurologic (e.g., ataxia, polyneuropathy, epilepsy, learning and developmental delay, spastic diplegia) •microcephaly •growth retardation	AR	[33,38,39,40,41,42,43]
ERAL1 (17q11.2)	Era like 12S mitochondrial rRNA chaperone 1	mitochondrial	mitochondrial protein translation (assembly of mitochondrial ribosomal subunit)	•not reported	AR	[44]
GGPS1 (1q42.3)	geranylgeranyl diphosphate synthase 1	cytoplasmic	acts on peroxisomal products, part of mevalonate pathway	•neurologic (muscular dystrophy, myopathy)	AR	[33,45]
HARS2 (5q31.3)	histidyl-tRNA synthetase 2	mitochondrial	mitochondrial protein translation (synthesis of histidyl-transfer RNA)	•not reported	AR	[39,46,47]
HSD17B4 (17q21.2)	hydroxysteroid 17-β dehydrogenase 4	peroxisomal	β-oxidation pathway for fatty acids in peroxisomes	•neurologic (e.g., ataxia, polyneuropathy, cerebellar atrophy, spastic diplegia, hypertonia, dysarthria, nystagmus, oculomotor apraxia, tremor, delayed motor development, cognitive impairment) •growth retardation •skeletal (e.g., pes cavus, pes equinovarus, scoliosis)	AR	[39,41,48,49,50,51]
LARS2 (3p21.31)	leucyl-tRNA synthetase	mitochondrial	mitochondrial protein translation (synthesis of leucyl-transfer RNA)	•neurologic (e.g., ataxia, cerebellar syndrome, epilepsy, developmental delay, intellectual impairment, behavior disorder, leukodystrophy) •macrocephaly	AR	[33,39,41,52,53,54,55,56,57,58,59,60]
PEX6 (6p21.1)	peroxisomal biogenesis factor 6	peroxisomal	peroxisomal protein import (ATPase activity)	•not reported	AR	[33]
RMND1 (6q25.1)	required for meiotic nuclear division 1 homolog	mitochondrial	mitochondrial protein translation	•kidney disease •short stature	AR	[6] Present study
TFAM (10q21.1)	transcription factor A, mitochondrial	mitochondrial	key mitochondrial transcription factor	•intellectual impairment	AR	[33]
TWNK (10q24.31)	twinkle mtDNA helicase	mitochondrial	mitochondrial DNA replication and transcription (unwinds double-stranded DNA)	•neurologic (e.g., ataxia, polyneuropathy, limb paresis, muscle atrophy, muscle weakness, atrophy of cerebellum, diminished cervical enlargement, epilepsy, impaired eye movements, nystagmus, dysarthria)	AR	[39,41,61,62,63,64,65]

* Clinical features additional to hearing loss (HL) and ovarian dysfunction observed in some patients. AR, autosomal recessive.