Wide diagnostic and genotypic spectrum in patients with suspected mitochondrial disease

Orphanet Journal of Rare Diseases

Research

Birutė Burnytė¹  Kristina Grigalionienė¹  Algirdas Utkus¹  Laima Ambrozaitytė¹ 

[1] Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Santariškių Str. 2, LT-08661, Vilnius, Lithuania;

关键词: Mitochondrial disease;    mtDNA;    nDNA;    Genetic diagnosis;    Variants;    Next generation sequencing;    Whole exome sequencing;   

DOI  :  10.1186/s13023-023-02921-0

 received in 2023-04-25, accepted in 2023-09-21,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMitochondrial Diseases (MDs) are a diverse group of neurometabolic disorders characterized by impaired mitochondrial oxidative phosphorylation and caused by pathogenic variants in more than 400 genes. The implementation of next-generation sequencing (NGS) technologies helps to increase the understanding of molecular basis and diagnostic yield of these conditions. The purpose of the study was to investigate diagnostic and genotypic spectrum in patients with suspected MD. The comprehensive analysis of mtDNA variants using Sanger sequencing was performed in the group of 83 unrelated individuals with clinically suspected mitochondrial disease. Additionally, targeted next generation sequencing or whole exome sequencing (WES) was performed for 30 patients of the study group.ResultsThe overall diagnostic rate was 21.7% for the patients with suspected MD, increasing to 36.7% in the group of patients where NGS methods were applied. Mitochondrial disease was confirmed in 11 patients (13.3%), including few classical mitochondrial syndromes (MELAS, MERRF, Leigh and Kearns-Sayre syndrome) caused by pathogenic mtDNA variants (8.4%) and MDs caused by pathogenic variants in five nDNA genes. Other neuromuscular diseases caused by pathogenic variants in seven nDNA genes, were confirmed in seven patients (23.3%).ConclusionThe wide spectrum of identified rare mitochondrial or neurodevelopmental diseases proves that MD suspected patients would mostly benefit from an extensive genetic profiling allowing rapid diagnostics and improving the care of these patients.

【 授权许可】

CC BY   
© Institut National de la Santé et de la Recherche Médicale (INSERM) 2023