Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review

Mitochondrial encephalomyopathies (MEMP) are heterogeneous multisystem disorders frequently associated with mitochondrial DNA (mtDNA) mutations. Clinical presentation varies considerably in age of onset, course, and severity up to death in early childhood. In this study, we performed molecular genet...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Phepy G. A. Dawod, Jasna Jancic, Ana Marjanovic, Marija Brankovic, Milena Jankovic, Janko Samardzic, Ayman Gamil Anwar Dawod, Ivana Novakovic, Fayda I. Abdel Motaleb, Vladimir Radlovic, Vladimir S. Kostic, Dejan Nikolic
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	MELAS leigh syndrome mtDNA sanger sequencing mutations haplogroups Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/efad65c1e5054e169c32f3dbdc13deda
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:efad65c1e5054e169c32f3dbdc13deda
record_format	dspace
spelling	oai:doaj.org-article:efad65c1e5054e169c32f3dbdc13deda2021-11-25T17:20:20ZMutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review10.3390/diagnostics111119692075-4418https://doaj.org/article/efad65c1e5054e169c32f3dbdc13deda2021-10-01T00:00:00Zhttps://www.mdpi.com/2075-4418/11/11/1969https://doaj.org/toc/2075-4418Mitochondrial encephalomyopathies (MEMP) are heterogeneous multisystem disorders frequently associated with mitochondrial DNA (mtDNA) mutations. Clinical presentation varies considerably in age of onset, course, and severity up to death in early childhood. In this study, we performed molecular genetic analysis for mtDNA pathogenic mutation detection in Serbian children, preliminary diagnosed clinically, biochemically and by brain imaging for mitochondrial encephalomyopathies disorders. Sanger sequencing analysis in three Serbian probands revealed two known pathogenic mutations. Two probands had a heteroplasmic point mutation m.3243A>G in the <i>MT-TL1</i> gene, which confirmed mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode syndrome (MELAS), while a single case clinically manifested for Leigh syndrome had an almost homoplasmic (close to 100%) m.8993T>G mutation in the <i>MT-ATP6</i> gene. After full mtDNA MITOMASTER analysis and PhyloTree build 17, we report MELAS’ association with haplogroups U and H (U2e and H15 subclades); likewise, the mtDNA-associated Leigh syndrome proband shows a preference for haplogroup H (H34 subclade). Based on clinical–genetic correlation, we suggest that haplogroup H may contribute to the mitochondrial encephalomyopathies’ phenotypic variability of the patients in our study. We conclude that genetic studies for the distinctive mitochondrial encephalomyopathies should be well-considered for realizing clinical severity and possible outcomes.Phepy G. A. DawodJasna JancicAna MarjanovicMarija BrankovicMilena JankovicJanko SamardzicAyman Gamil Anwar DawodIvana NovakovicFayda I. Abdel MotalebVladimir RadlovicVladimir S. KosticDejan NikolicMDPI AGarticleMELASleigh syndromemtDNAsanger sequencingmutationshaplogroupsMedicine (General)R5-920ENDiagnostics, Vol 11, Iss 1969, p 1969 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	MELAS leigh syndrome mtDNA sanger sequencing mutations haplogroups Medicine (General) R5-920
spellingShingle	MELAS leigh syndrome mtDNA sanger sequencing mutations haplogroups Medicine (General) R5-920 Phepy G. A. Dawod Jasna Jancic Ana Marjanovic Marija Brankovic Milena Jankovic Janko Samardzic Ayman Gamil Anwar Dawod Ivana Novakovic Fayda I. Abdel Motaleb Vladimir Radlovic Vladimir S. Kostic Dejan Nikolic Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review
description	Mitochondrial encephalomyopathies (MEMP) are heterogeneous multisystem disorders frequently associated with mitochondrial DNA (mtDNA) mutations. Clinical presentation varies considerably in age of onset, course, and severity up to death in early childhood. In this study, we performed molecular genetic analysis for mtDNA pathogenic mutation detection in Serbian children, preliminary diagnosed clinically, biochemically and by brain imaging for mitochondrial encephalomyopathies disorders. Sanger sequencing analysis in three Serbian probands revealed two known pathogenic mutations. Two probands had a heteroplasmic point mutation m.3243A>G in the <i>MT-TL1</i> gene, which confirmed mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode syndrome (MELAS), while a single case clinically manifested for Leigh syndrome had an almost homoplasmic (close to 100%) m.8993T>G mutation in the <i>MT-ATP6</i> gene. After full mtDNA MITOMASTER analysis and PhyloTree build 17, we report MELAS’ association with haplogroups U and H (U2e and H15 subclades); likewise, the mtDNA-associated Leigh syndrome proband shows a preference for haplogroup H (H34 subclade). Based on clinical–genetic correlation, we suggest that haplogroup H may contribute to the mitochondrial encephalomyopathies’ phenotypic variability of the patients in our study. We conclude that genetic studies for the distinctive mitochondrial encephalomyopathies should be well-considered for realizing clinical severity and possible outcomes.
format	article
author	Phepy G. A. Dawod Jasna Jancic Ana Marjanovic Marija Brankovic Milena Jankovic Janko Samardzic Ayman Gamil Anwar Dawod Ivana Novakovic Fayda I. Abdel Motaleb Vladimir Radlovic Vladimir S. Kostic Dejan Nikolic
author_facet	Phepy G. A. Dawod Jasna Jancic Ana Marjanovic Marija Brankovic Milena Jankovic Janko Samardzic Ayman Gamil Anwar Dawod Ivana Novakovic Fayda I. Abdel Motaleb Vladimir Radlovic Vladimir S. Kostic Dejan Nikolic
author_sort	Phepy G. A. Dawod
title	Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review
title_short	Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review
title_full	Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review
title_fullStr	Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review
title_full_unstemmed	Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review
title_sort	mutational analysis and mtdna haplogroup characterization in three serbian cases of mitochondrial encephalomyopathies and literature review
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/efad65c1e5054e169c32f3dbdc13deda
work_keys_str_mv	AT phepygadawod mutationalanalysisandmtdnahaplogroupcharacterizationinthreeserbiancasesofmitochondrialencephalomyopathiesandliteraturereview AT jasnajancic mutationalanalysisandmtdnahaplogroupcharacterizationinthreeserbiancasesofmitochondrialencephalomyopathiesandliteraturereview AT anamarjanovic mutationalanalysisandmtdnahaplogroupcharacterizationinthreeserbiancasesofmitochondrialencephalomyopathiesandliteraturereview AT marijabrankovic mutationalanalysisandmtdnahaplogroupcharacterizationinthreeserbiancasesofmitochondrialencephalomyopathiesandliteraturereview AT milenajankovic mutationalanalysisandmtdnahaplogroupcharacterizationinthreeserbiancasesofmitochondrialencephalomyopathiesandliteraturereview AT jankosamardzic mutationalanalysisandmtdnahaplogroupcharacterizationinthreeserbiancasesofmitochondrialencephalomyopathiesandliteraturereview AT aymangamilanwardawod mutationalanalysisandmtdnahaplogroupcharacterizationinthreeserbiancasesofmitochondrialencephalomyopathiesandliteraturereview AT ivananovakovic mutationalanalysisandmtdnahaplogroupcharacterizationinthreeserbiancasesofmitochondrialencephalomyopathiesandliteraturereview AT faydaiabdelmotaleb mutationalanalysisandmtdnahaplogroupcharacterizationinthreeserbiancasesofmitochondrialencephalomyopathiesandliteraturereview AT vladimirradlovic mutationalanalysisandmtdnahaplogroupcharacterizationinthreeserbiancasesofmitochondrialencephalomyopathiesandliteraturereview AT vladimirskostic mutationalanalysisandmtdnahaplogroupcharacterizationinthreeserbiancasesofmitochondrialencephalomyopathiesandliteraturereview AT dejannikolic mutationalanalysisandmtdnahaplogroupcharacterizationinthreeserbiancasesofmitochondrialencephalomyopathiesandliteraturereview
_version_	1718412505365086208

Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review

Ejemplares similares