What question did this study set out to answer?

This report aims to expand understanding of the clinical spectrum associated with MGME1-related mitochondrial disease.

January 10, 2026American Journal of Medical Genetics Part A0 citationsOpen Access

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

NANazli Busra AcikgozHacettepe University GDGizem Urel DemirHacettepe University YYYilmaz YildizHacettepe University

Key Result

A homozygous MGME1 variant was identified in Turkish siblings, with one sibling successfully undergoing heart transplantation due to progressive dilated cardiomyopathy.

Key Points

This report aims to expand understanding of the clinical spectrum associated with MGME1-related mitochondrial disease.
Identified homozygous MGME1 variant using whole exome sequencing (WES).
Confirmed homozygosity through Sanger sequencing.
Documented clinical symptoms including ptosis, myopathy, and scoliosis.
Reviewed the clinical course leading to orthotopic heart transplantation.
Both siblings exhibited symptoms typical of MGME1-related disease.
The index patient underwent successful heart transplantation due to severe cardiomyopathy.
The MGME1 variant was classified as a variant of uncertain significance, highlighting the need for functional studies.

Structured PICO

Population

Two Turkish siblings harboring a homozygous MGME1 variant (NM_052865.4:c.818 T>A; p.(Val273Glu)), presenting with ptosis, myopathy, scoliosis, and gastrointestinal symptoms, with the index patient developing progressive, medically refractory dilated cardiomyopathy.

Intervention

Orthotopic heart transplantation (OHT) and genomic data reanalysis (WES and Sanger sequencing)

Outcome

Clinical course including successful orthotopic heart transplantation and identification of the genetic variant

This report expands the clinical spectrum of MGME1-related mitochondrial disease to include dilated cardiomyopathy requiring heart transplantation and highlights the importance of periodic genomic data reanalysis.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

ABSTRACT We report two siblings harboring a homozygous MGME1 variant, NM₀52865. 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.

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