Paediatric or syndromic cardiomyopathy

Gene: MTO1

Green List (high evidence)

Comment on list classification: There are > 30 cases reported with biallelic MTO1 variants and hypertrophic cardiomyopathy as one of the hallmark presentations. Hence, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.

Created: 29 Aug 2025, 2:14 p.m. | Last Modified: 29 Aug 2025, 2:14 p.m.

Panel Version: 7.40

Comment on phenotypes: This gene has been associated with relevant phenotypes in both OMIM (MIM #614702) and Gene2Phenotype (with 'definitive' rating on the DD panel). OMIM phenotype was accessed on 29 August 2025.

Created: 29 Aug 2025, 2:13 p.m. | Last Modified: 29 Aug 2025, 2:13 p.m.

Panel Version: 7.39

PMID:22608499 (2012) reported two infant siblings and an unrelated child of Italian descent with hypertrophic cardiomyopathy and neonatal lactic acidosis. The siblings died early in their life (when 19 days and 40 days old). The affected siblings were identified with compound heterozygous variants in MTO1 gene – a maternal frameshift variant (c.1858dup/ p.Arg620Lysfs(∗)8) and a paternal missense variant (c.1282G>A/ p.Ala428Thr). The unrelated patient was homozygous for the same missense variant (c.1282G>A).

PMID:23929671 (2013) reported five additional patients from three unrelated families, who also presented with hypertrophic cardiomyopathy and lactic acidosis, in addition to other variable phenotypes including psychomotor delay, hypotonia, feeding difficulties and respiratory illness. The two sibling pairs were identified with homozygous missense variants (c.1232C>T/ p.Thr411Ile), while the unrelated patient was reported with compound heterozygous missense variants (c.1402G>A/ p.Ala428Thr & c.1430G>A/ p.Arg477His).

PMID:34547275 (2021) reported the identification of compound heterozygous variants in MTO1 gene in a Chinese patient with complex oxidative phosphorylation deficiency type 10 (COXPD10). This patient had lactic acidosis and cardia abnormalities such as myocarditis and tachycardia, but not hypertrophic cardiomyopathy. The identified variants are c.344delA (p.Asn115Thrfs*11, frameshift) and c.1055C>T (p.Thr352Met, missense).

PMID:34990597 (2022) reported a patient with COXPD10 presenting with multiple organ failure, severe pneumonia, sepsis, hyperlactatemia, metabolic acidosis, and moderate anaemia. The patient was identified with compound heterozygous variants in MTO1 gene (c.1291C > T/ p.Arg431Trp and c.1390C > T/ p.Arg464Cys). The patient also showed HCM. This study also reviewed previously published cases of confirmed MTO1 deficiency. Of 42 total cases including the patient reported in this study, 32 patients were reported with HCM and one additional patient was reported with dilated cardiomyopathy.

PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the 100,000 genomes project, of which one patient with unspecified cardiomyopathy was identified with compound heterozygous missense variants in MTO1 gene (c.938G>C/ p.Arg313Pro & c.1232C>T/ p.Thr411Ile).

There is also functional evidence available in support of the disease association.
Sources: Literature

Created: 29 Aug 2025, 2:11 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency 10, OMIM:614702; mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency, MONDO:0013865

Publications

• 22608499
• 23929671
• 34547275
• 34990597
• 39472908