Homozygous MGME1 Variant in Turkish Siblings: First Reported Case With Successful Heart Transplantation, Expanding the Clinical Spectrum of MGME1-Related Mitochondrial Disease
American Journal of Medical Genetics, Part A, cilt.200, sa.5, ss.1128-1133, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 200 Sayı: 5
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/ajmga.70049
- Dergi Adı: American Journal of Medical Genetics, Part A
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE
- Sayfa Sayıları: ss.1128-1133
- Anahtar Kelimeler: dilated cardiomyopathy, heart transplantation, MGME1, mitochondrial DNA depletion syndrome 11, reanalyze, whole exome sequencing
- Hacettepe Üniversitesi Adresli: Evet
Özet
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.