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Whole mitochondrial genome analysis in two families with dilated mitochondrial cardiomyopathy : detection of mutations in MT-ND2 and MT-TL1 genes

Alila, Olfa Fersi; Rebai, Emna Mkaouar; Tabebi, Mouna; Tej, Amel; Chamkha, Imen LU ; Tlili, Abdelaziz; Bouguila, Jihene; Tilouche, Samia; Soyah, Nejla and Boughamoura, Lamia, et al. (2016) In Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis 27(4). p.80-2873
Abstract

Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause cardiomyopathy and heart failure. These mutations were described in the mt-tRNA genes and in the mitochondrial protein-coding genes. The aim of this study was to identify the genetic defect in two patients belonging to two families with cardiac dysfunction associated to a wide spectrum of clinical phenotypes. The sequencing analysis of the whole mitochondrial DNA in the two patients and their parents revealed the presence of known polymorphisms associated to cardiomyopathy and two pathogenic mutations in DNA extracted from blood leucocytes: the heteroplasmic m.3243A > G mutation in the MT-TL1 gene in patient A; and the homoplasmic m.5182C... (More)

Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause cardiomyopathy and heart failure. These mutations were described in the mt-tRNA genes and in the mitochondrial protein-coding genes. The aim of this study was to identify the genetic defect in two patients belonging to two families with cardiac dysfunction associated to a wide spectrum of clinical phenotypes. The sequencing analysis of the whole mitochondrial DNA in the two patients and their parents revealed the presence of known polymorphisms associated to cardiomyopathy and two pathogenic mutations in DNA extracted from blood leucocytes: the heteroplasmic m.3243A > G mutation in the MT-TL1 gene in patient A; and the homoplasmic m.5182C > T mutation in the ND2 gene in patient B. Secondary structure analysis of the ND2 protein further supported the deleterious role of the m.5182C > T mutation, as it was found to be involved an extended imbalance in its hydrophobicity and affect its function. In addition, the mitochondrial variants identified in patients A and B classify both of them in the same haplogroup H2a2a1.

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Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis
volume
27
issue
4
pages
8 pages
external identifiers
  • Scopus:84939190695
DOI
10.3109/19401736.2015.1060417
language
English
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no
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cd19beb4-df65-4379-aeb4-06d7fc0c281f
date added to LUP
2016-09-14 12:07:31
date last changed
2016-10-13 05:13:28
@misc{cd19beb4-df65-4379-aeb4-06d7fc0c281f,
  abstract     = {<p>Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause cardiomyopathy and heart failure. These mutations were described in the mt-tRNA genes and in the mitochondrial protein-coding genes. The aim of this study was to identify the genetic defect in two patients belonging to two families with cardiac dysfunction associated to a wide spectrum of clinical phenotypes. The sequencing analysis of the whole mitochondrial DNA in the two patients and their parents revealed the presence of known polymorphisms associated to cardiomyopathy and two pathogenic mutations in DNA extracted from blood leucocytes: the heteroplasmic m.3243A &gt; G mutation in the MT-TL1 gene in patient A; and the homoplasmic m.5182C &gt; T mutation in the ND2 gene in patient B. Secondary structure analysis of the ND2 protein further supported the deleterious role of the m.5182C &gt; T mutation, as it was found to be involved an extended imbalance in its hydrophobicity and affect its function. In addition, the mitochondrial variants identified in patients A and B classify both of them in the same haplogroup H2a2a1.</p>},
  author       = {Alila, Olfa Fersi and Rebai, Emna Mkaouar and Tabebi, Mouna and Tej, Amel and Chamkha, Imen and Tlili, Abdelaziz and Bouguila, Jihene and Tilouche, Samia and Soyah, Nejla and Boughamoura, Lamia and Fakhfakh, Faiza},
  language     = {eng},
  number       = {4},
  pages        = {80--2873},
  series       = {Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis},
  title        = {Whole mitochondrial genome analysis in two families with dilated mitochondrial cardiomyopathy : detection of mutations in MT-ND2 and MT-TL1 genes},
  url          = {http://dx.doi.org/10.3109/19401736.2015.1060417},
  volume       = {27},
  year         = {2016},
}