Open AccessThe first concurrent detection of mitochondrial DNA m.3243A>G mutation, deletion, and depletion in a family with mitochondrial diabetes
Author(s) -
Tabebi Mouna,
Safi Wajdi,
Felhi Rahma,
Alila Fersi Olfa,
Keskes Leila,
Abid Mohamed,
Mnif Mouna,
Fakhfakh Faiza
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1292
Subject(s) - heteroplasmy , mitochondrial dna , genetics , proband , point mutation , mitochondrial disease , mutation , non mendelian inheritance , biology , melas syndrome , mitochondrial encephalomyopathy , mitochondrial myopathy , medicine , gene
Background Mitochondrial diabetes (MD) is a rare monogenic form of diabetes and divided into type l and type 2. It is characterized by a strong familial clustering of diabetes with the presence of maternal transmission in conjunction with bilateral hearing impairment in most of the carriers. The most common form of MD is associated with the m.3243A>G mutation in the mitochondrial MT‐TL1 , but there are also association with a range of other point mutations, deletion, and depletion in mtDNA. Methods The mitochondrial genome anomalies were investigated in a family with clinical features of MD, which includes a proband presenting severe MD conditions including cardiomyopathy, retinopathy, and psychomotor retardation. Results By investigating the patient's blood leukocytes and skeletal muscle, we identified the m.3243A>G mutation in heteroplasmic state. This mutation was absent in the rest of the family members. In addition, our analysis revealed in the proband a large mtDNA heteroplasmic deletion (~1 kb) and a reduction in mtDNA copy number. Conclusion Our study points out, for the first time, a severe phenotypic expression of the m.3243A>G point mutation in association with mtDNA deletion and depletion in MD.