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Page 78 Webb et al. J Transl Genet Genom 2020;4:71-80 I https://doi.org/10.20517/jtgg.2020.11

At present, nine MRPS genes and three MRPL genes have been identified to cause mitochondrial disease in
humans [Table 3]. All are inherited in an autosomal recessive fashion. Mutations in mitochondrial ribosomal
protein genes may destabilize the mitoribosomal subunits impacting translation, as has been shown via
[44]
proteomic analysis with MRPS34 disorder . Despite the presumptive shared pathogenesis of destabilizing
either the large or small mitoribosomal subunits, the clinical phenotypes associated with mutations in genes
encoding mitoribosomal structural proteins are surprisingly diverse [Table 3]. Most of these disorders
present early in life, although missense mutations in MRPS22 can present with ovarian failure in adolescent
[45]
females . Neurological deficits have been observed in the majority of patients with this subset of disorders
but additional associated clinical phenotypes include hepatopathy, renal dysfunction, deafness, myopathy,
and craniofacial or cardiac phenotypes. The neurological features may be variable and range from structural
lesions such as agenesis of the corpus callosum to classical Leigh syndrome or functional deficits without
apparent structural lesions. Most mitochondrial ribosomal protein subunit disorders cause severe disease
often with multi-organ involvement and early death. In the future, additional mitochondrial ribosomal
protein disorders are highly likely to be identified via whole exome sequencing of patients with suspected
mitochondrial disease.

CONCLUSION
Defects in mitochondrial translation may result in a vast array of clinical disease. Disease mechanisms
include, but are not limited to, mitochondrial tRNA mutations, mitochondrial aminoacyl-tRNA synthetase
mutations, mitochondrial rRNA mutations, and mitochondrial ribosomal protein mutations. Understanding
disease biology of these mitochondrial translation defects is a necessary predecessor to developing effective
treatment for these disorders. More research is necessary to further understand this emerging class of
mitochondrial disease.

DECLARATIONS
Authors’ contributions
Reviewed literature, wrote manuscript, and edited manuscript: Webb BD, Diaz GA, Prasun P

Availability of data and materials
Not applicable.

Financial support and sponsorship
Dr. Bryn D. Webb receives support from National Institutes of Health National Institute of Child Health and
Human Development (K08HD086827).

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

REFERENCES
1. Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB, et al. A mitochondrial protein compendium elucidates complex I disease biology.
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