Homozygous MGME1 Variant in Turkish Siblings: First Reported Case With Successful Heart Transplantation, Expanding the Clinical Spectrum of MGME1-Related Mitochondrial Disease

Acikgoz N. B., Demir G. U., YILDIZ Y., Duz M. B., Sener N., ALPAT Ş., ...More

American Journal of Medical Genetics, Part A, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2026
  • Doi Number: 10.1002/ajmga.70049
  • Journal Name: American Journal of Medical Genetics, Part A
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE
  • Keywords: dilated cardiomyopathy, heart transplantation, MGME1, mitochondrial DNA depletion syndrome 11, reanalyze, whole exome sequencing
  • Hacettepe University Affiliated: Yes

Abstract

We report two siblings harboring a homozygous MGME1 variant, NM_052865.4:c.818 T>A; p.(Val273Glu), both presenting with ptosis, myopathy, scoliosis, and gastrointestinal symptoms. The index patient developed progressive, medically refractory dilated cardiomyopathy and underwent successful orthotopic heart transplantation (OHT). Reanalysis of previously negative WES identified the variant in the index case, and segregation by Sanger sequencing confirmed homozygosity in both siblings. Although several clinical findings overlap with previously described MGME1-related disease, the detected variant remains classified as a variant of uncertain significance (VUS); thus, functional evidence is needed to better understand its potential causal relevance. Additionally, this report underscores the importance of periodic genomic data reanalysis and highlights the variable expressivity that may occur even within the same family.