Paediatric or syndromic cardiomyopathy

Gene: TKFC

I don't know

Comment on list classification: Three unrelated cases reported with TKFC variants (two missense and one nonsense) and cardiomyopathy. However, the phenotype did not completely segregate with variant in one family.

This gene should be rated amber with the current evidence. The 'watchlist' tag has been added to review the gene in future in light of new evidence.

Created: 1 Sep 2025, 9:13 p.m. | Last Modified: 1 Sep 2025, 9:13 p.m.

Panel Version: 7.65

PMID:32004446 (2020) reported four affected individuals from 2 consanguineous families with congenital cataracts, developmental delay, liver dysfunction and microcytic anaemia. One of the infants also had fatal dilated cardiomyopathy (DCM) and lactic acidosis following a febrile illness. Both families were identified with homozygous missense variants in TKFC gene, and c.1628G>T (p.Arg543Ile) variant was present in the infant with DCM.

PMID:39251934 (2024) reported two deceased neonate siblings presenting with oculocutaneous albinism type1 (OCA1). They had severe skeletal abnormalities and fatal hypertrophic cardiomyopathy (HCM). Upon performing WES and segregation analysis, positive co-segregation of nonsense homozygous c.346C > T (p.Arg116Ter) variant in TYR gene and missense homozygous c.598G > A (p.Val200Ile) variant in TKFC gene were identified in the two affected patients.

PMID:39472908 (2024) reported paediatric and adult probands with diverse cardiomyopathies from the UK 100,000 genomes project cohort, of which one paediatric patient with DCM was identified with homozygous missense variant in TKFC gene (c.1628G>T/ p.Arg543Ile) via reanalysis of data from trio genome sequencing. This variant is reported as likely pathogenic and the publication states that the phenotype is explained by the genotype.

This gene has been associated with Triokinase and FMN cyclase deficiency syndrome (MIM #618805) in OMIM (phenotype accessed in OMIM on 01 September 2025), which includes DCM as one of the clinical manifestations.
Sources: Literature

Created: 1 Sep 2025, 9:09 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Triokinase and FMN cyclase deficiency syndrome, OMIM:618805; triokinase and FMN cyclase deficiency syndrome, MONDO:0032927; cardiomyopathy, MONDO:0004994

Publications

• 32004446
• 39251934
• 39472908