A Mild Phenotype of Mitochondrial DNA Depletion Syndrome Type 13 with a Novel FBXL4 Variant

Oncul U., Kose E., EMİNOĞLU F. T.

MOLECULAR SYNDROMOLOGY, vol.12, no.5, pp.294-299, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 12 Issue: 5
  • Publication Date: 2021
  • Doi Number: 10.1159/000515928
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE
  • Page Numbers: pp.294-299
  • Keywords: Encephalopathy, FBXL4, Mitochondrial DNA depletion, mtDNA depletion syndrome, Myopathy, MTDPS13, MUTATIONS
  • Dokuz Eylül University Affiliated: No


Mitochondrial DNA depletion syndromes (MDDS) are a group of rare genetic disorders caused by defects in multiple genes involved in mitochondrial DNA maintenance. Among these, FBXL4 gene variants result in encephalomyopathic mtDNA depletion syndrome 13 (MTDPS13), which commonly presents as a combination of failure to thrive, neurodevelopmental delays, encephalopathy, hypotonia, a pattern of mild facial dysmorphisms, and persistent lactic acidosis. To date, 53 pathogenic FBXL4 variants and 100 cases have been described in the literature. In the present case report, we report on a 4.5-year-old boy with MTDPS13 and a novel variant. The patient had a history of antenatal hydrocephalus, severe developmental delay and mental motor retardation with psychomotor delay, severe hypotonia, mild left ventricular hypertrophic cardiomyopathy, mild facial dysmorphism, and elevated lactate levels. Symptoms suggested mitochondrial myopathy; subsequently, whole-exome sequencing was performed and a novel homozygous variant FBXL4 (NM_012160.4): c.486T>G (p.Tyr162Ter) was identified. While most of the patients with FBLX4 gene mutation have severe clinical manifestation and die at a very young age, clinical progress of our case was milder than previously reported. MDDS are very rare and can present with many different clinical signs and symptoms. In this report, we identified a novel pathogenic variant in the FBXL4 gene. This report shows that patients with FBLX4 gene mutations may present with a milder clinical phenotype than previously reported.