Likely inborn error of metabolism

Gene: MRPS23

Green List (high evidence)

Comment on phenotypes: OMIM phenotype updated 14th May 2026.

Created: 14 May 2026, 4:28 p.m. | Last Modified: 14 May 2026, 4:28 p.m.

Panel Version: 9.4

Comment on list classification: There are now 3 unrelated cases with biallelic MRPS23 missense variants and a Combined oxidative phosphorylation deficiency (defects in CI and CIV shown in fibroblast cultures). Hence, this gene should be promoted to Green at the next GMS update.

Created: 14 May 2026, 4:26 p.m. | Last Modified: 14 May 2026, 4:26 p.m.

Panel Version: 9.2

Additional cases:
PMID: 41506652 Mandia et al., 2026
Male proband B:II:1 with variant in MRPS23 (NM_016070.4):c.119C>T, p.(Pro40Leu) - homozygous. Individual exhibited leukoencephalopathy with distinctive white matter abnormalities, intellectual impairment, sensorineural deafness, cerebellar ataxia, pyramidal syndrome, and amyotrophic weakness in distal limbs, attributed to distal motor neuropathy. Folinic acid treatment resulted in great improvement. Fibroblast analysis showed a decrease in expression of complex I and IV subunits.

PMID: 38086984 Ittiwut et al., 2023
Report of five independent patients who had similar clinical manifestations and were homozygous for the same germline variant c.119C>T; p.P40L in MRPS23 - all from Hmong hilltribe (Thailand) - likely founder variant, estimated to have occured 1550 yrs ago. The variant is found in 2 heterozygotes in gnomAD v4.1.1.
Patients showed delayed growth and development, hearing impairment, hypoglycemia, lactic acidosis, and liver dysfunction. 1 individual had severe hearing impairment. In vitro assays of cultured fibroblasts showed combined respiratory chain complex deficiency with low activities of complexes I and IV.

Created: 14 May 2026, 4:25 p.m. | Last Modified: 14 May 2026, 4:25 p.m.

Panel Version: 9.1

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Combined oxidative phosphorylation deficiency 46, OMIM:618952; combined oxidative phosphorylation deficiency 46, MONDO:0033534

Publications

• 38086984
• 41506652

Red List (low evidence)

No further variants have been reported in the literature to date (21/10/2019).

Created: 21 Oct 2019, 3:04 p.m. | Last Modified: 21 Oct 2019, 3:04 p.m.

Panel Version: 1.372

No further cases have been found for this gene; therefore, this gene will remain a red gene until further evidence is available.

Created: 2 May 2019, 12:34 p.m.

Comment on list classification: Single case in the literature therefore this should be a red gene - PMID: 26741492 describes the finding of a 500kb region of homozygosity encompassing the MRPS23 gene within a boy with hepatic disease and combined respiratpry chain complex deficiencies. The patient was homozygous for the candidate variant c.119C>G p.P40R (both parents were heterozygous). In vitro complementation assays resuced defects in complexes I and IV, and restored motochondrial 12S rRNA/16S rRNA expression.

Created: 15 Feb 2016, 2:40 p.m.

Green List (high evidence)

single mutation report in literature

Created: 7 Feb 2016, 8:37 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal