Biallelic potential disease-causing missense variants in TAF1A in two siblings with infantile restrictive cardiomyopathy

Eur J Med Genet. 2024 Oct:71:104968. doi: 10.1016/j.ejmg.2024.104968. Epub 2024 Aug 28.

Abstract

TAF1A, a gene encoding a TATA-box binding protein involved in ribosomal RNA synthesis, is a candidate gene for pediatric cardiomyopathy as biallelic TAF1A variants were reported in two families with affected individuals. Here, we report a third family with two siblings who presented with infantile restrictive cardiomyopathy and carried biallelic missense variants in TAF1A (NM_001201536.1:c.1021G>A p.(Gly341Arg) and c.781A>C p.(Thr261Pro)). Additional shared clinical features in the siblings included feeding intolerance, congenital leukoencephalopathy, ventriculomegaly and concern for primary immunodeficiency. The first-born sibling passed away at 6 months of age due to complications of hemophagocytic lymphohistiocytosis (HLH) whereas the second sibling underwent cardiac transplantation at 1 year of age and is currently well. We compare the clinical and molecular features of all the TAF1A associated cardiomyopathy cases. Our study adds evidence for the gene-disease association of TAF1A with autosomal recessive pediatric cardiomyopathy.

Keywords: Autosomal recessive; Cardiac transplant; Dilated cardiomyopathy; Pediatric cardiomyopathy; Restrictive cardiomyopathy; Ribosomal RNA synthesis; Ribosomopathy; TAF1A.

Publication types

  • Case Reports

MeSH terms

  • Alleles
  • Cardiomyopathy, Restrictive* / genetics
  • Cardiomyopathy, Restrictive* / pathology
  • Female
  • Histone Acetyltransferases
  • Humans
  • Infant
  • Male
  • Mutation, Missense*
  • Pedigree
  • Phenotype
  • Siblings*
  • TATA-Binding Protein Associated Factors* / genetics
  • Transcription Factor TFIID* / genetics

Substances

  • TATA-Binding Protein Associated Factors
  • Transcription Factor TFIID
  • TATA-binding protein associated factor 250 kDa
  • Histone Acetyltransferases