A case of ATR-X syndrome with mitochondrial respiratory chain dysfunction

Eur J Med Genet. 2021 Aug;64(8):104251. doi: 10.1016/j.ejmg.2021.104251. Epub 2021 May 27.

Abstract

Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by a mutation in ATRX, which is essential for proper chromatin remodeling. ATRX dysfunction leads to dysregulation of many genes due to abnormal chromatin remodeling, and causes a multisystem disorder in patients with ATR-X. Because mitochondrial disorders also show multisystem involvement, whether mitochondrial function is affected in patients with ATR-X is of interest. Here, we report a case of a 4-year-old male with a mutation (NM_000489.4: c.736C > T p.Arg246Cys) in ATRX, who showed mitochondrial dysfunction with complex I deficiency. The results from our study suggest that target genes of the ATRX protein may include those responsible for mitochondrial function, and mitochondrial dysfunction may contribute to some ATR-X phenotypes.

Keywords: ATR-X syndrome; Chromatin regulation; Mitochondrial respiratory chain disorders.

Publication types

  • Case Reports

MeSH terms

  • Cells, Cultured
  • Child, Preschool
  • Electron Transport Complex I / genetics
  • Electron Transport Complex I / metabolism*
  • Fibroblasts / metabolism
  • Humans
  • Male
  • Mental Retardation, X-Linked / genetics*
  • Mental Retardation, X-Linked / pathology
  • Mutation
  • X-linked Nuclear Protein / genetics*
  • alpha-Thalassemia / genetics*
  • alpha-Thalassemia / pathology

Substances

  • ATRX protein, human
  • X-linked Nuclear Protein
  • Electron Transport Complex I

Supplementary concepts

  • ATR-X syndrome