Mitochondrial DNA 11777C>A mutation associated leigh syndrome

Case report with a review of the previously described pedigrees

Kinga Hadzsiev, A. Maász, P. Kisfali, E. Kálmán, E. Gömöri, Endre Pal, Ervin Berenyi, K. Komlósi, B. Melegh

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Here, we present a male infant with clinical signs of typical Leigh syndrome. The first symptom, myoclonus was presented already on the 5th day of life; at 7 months of age limb convulsions and cerebral paresis with hypotonia were developed. At the age of 11 months, MRI verified increased signal intensity in the entire mesen-cephalon and medulla oblongata; while gray matter proton spectroscopy revealed presence of lactate increase in the brain. At age of 17 months, the child died in cardiorespi-ratory arrest. After autopsy, the diagnosis of Leigh syndrome was established; using DNA isolated from skeletal muscle and liver, heteroplasmic (>50%) mitochondrial 11777C>A was detected in the fourth subunit of NADH dehydrogenase enzyme (MTND4) encoding gene, which causes Arg → Ser replacement. The mutation was also detected in low copy number in blood of mother. Albeit this mutation type is well recognized as a typical mtDNA mutation, according the reports available on the PubMed, this mutation was described only in four patients with wide phenotypic variations; here, we reviewed the characteristic clinical features of them. Taken together, the earliest onset of symptoms, the nature of the first presentation signs, the most rapid progression, the character of minor additional symptoms, and the early fatal outcome differentiate the phenotypic variant of the proband presented here from cases reported so far by others.

Original languageEnglish
Pages (from-to)277-284
Number of pages8
JournalNeuroMolecular Medicine
Volume12
Issue number3
DOIs
Publication statusPublished - Sep 2010

Fingerprint

Leigh Disease
Pedigree
Mitochondrial DNA
Mutation
NADH Dehydrogenase
Medulla Oblongata
Myoclonus
Muscle Hypotonia
Fatal Outcome
Paresis
PubMed
Protons
Autopsy
Lactic Acid
Spectrum Analysis
Skeletal Muscle
Seizures
Extremities
Mothers
Liver

Keywords

  • Leigh syndrome
  • Mitochondrial DNA mtDNA 11777C> A
  • Mitochondrial mutation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Medicine
  • Neurology

Cite this

@article{48d15db157954ff8821e4d5813d1f5e3,
title = "Mitochondrial DNA 11777C>A mutation associated leigh syndrome: Case report with a review of the previously described pedigrees",
abstract = "Here, we present a male infant with clinical signs of typical Leigh syndrome. The first symptom, myoclonus was presented already on the 5th day of life; at 7 months of age limb convulsions and cerebral paresis with hypotonia were developed. At the age of 11 months, MRI verified increased signal intensity in the entire mesen-cephalon and medulla oblongata; while gray matter proton spectroscopy revealed presence of lactate increase in the brain. At age of 17 months, the child died in cardiorespi-ratory arrest. After autopsy, the diagnosis of Leigh syndrome was established; using DNA isolated from skeletal muscle and liver, heteroplasmic (>50{\%}) mitochondrial 11777C>A was detected in the fourth subunit of NADH dehydrogenase enzyme (MTND4) encoding gene, which causes Arg → Ser replacement. The mutation was also detected in low copy number in blood of mother. Albeit this mutation type is well recognized as a typical mtDNA mutation, according the reports available on the PubMed, this mutation was described only in four patients with wide phenotypic variations; here, we reviewed the characteristic clinical features of them. Taken together, the earliest onset of symptoms, the nature of the first presentation signs, the most rapid progression, the character of minor additional symptoms, and the early fatal outcome differentiate the phenotypic variant of the proband presented here from cases reported so far by others.",
keywords = "Leigh syndrome, Mitochondrial DNA mtDNA 11777C> A, Mitochondrial mutation",
author = "Kinga Hadzsiev and A. Ma{\'a}sz and P. Kisfali and E. K{\'a}lm{\'a}n and E. G{\"o}m{\"o}ri and Endre Pal and Ervin Berenyi and K. Koml{\'o}si and B. Melegh",
year = "2010",
month = "9",
doi = "10.1007/s12017-010-8115-9",
language = "English",
volume = "12",
pages = "277--284",
journal = "NeuroMolecular Medicine",
issn = "1535-1084",
publisher = "Humana Press",
number = "3",

}

TY - JOUR

T1 - Mitochondrial DNA 11777C>A mutation associated leigh syndrome

T2 - Case report with a review of the previously described pedigrees

AU - Hadzsiev, Kinga

AU - Maász, A.

AU - Kisfali, P.

AU - Kálmán, E.

AU - Gömöri, E.

AU - Pal, Endre

AU - Berenyi, Ervin

AU - Komlósi, K.

AU - Melegh, B.

PY - 2010/9

Y1 - 2010/9

N2 - Here, we present a male infant with clinical signs of typical Leigh syndrome. The first symptom, myoclonus was presented already on the 5th day of life; at 7 months of age limb convulsions and cerebral paresis with hypotonia were developed. At the age of 11 months, MRI verified increased signal intensity in the entire mesen-cephalon and medulla oblongata; while gray matter proton spectroscopy revealed presence of lactate increase in the brain. At age of 17 months, the child died in cardiorespi-ratory arrest. After autopsy, the diagnosis of Leigh syndrome was established; using DNA isolated from skeletal muscle and liver, heteroplasmic (>50%) mitochondrial 11777C>A was detected in the fourth subunit of NADH dehydrogenase enzyme (MTND4) encoding gene, which causes Arg → Ser replacement. The mutation was also detected in low copy number in blood of mother. Albeit this mutation type is well recognized as a typical mtDNA mutation, according the reports available on the PubMed, this mutation was described only in four patients with wide phenotypic variations; here, we reviewed the characteristic clinical features of them. Taken together, the earliest onset of symptoms, the nature of the first presentation signs, the most rapid progression, the character of minor additional symptoms, and the early fatal outcome differentiate the phenotypic variant of the proband presented here from cases reported so far by others.

AB - Here, we present a male infant with clinical signs of typical Leigh syndrome. The first symptom, myoclonus was presented already on the 5th day of life; at 7 months of age limb convulsions and cerebral paresis with hypotonia were developed. At the age of 11 months, MRI verified increased signal intensity in the entire mesen-cephalon and medulla oblongata; while gray matter proton spectroscopy revealed presence of lactate increase in the brain. At age of 17 months, the child died in cardiorespi-ratory arrest. After autopsy, the diagnosis of Leigh syndrome was established; using DNA isolated from skeletal muscle and liver, heteroplasmic (>50%) mitochondrial 11777C>A was detected in the fourth subunit of NADH dehydrogenase enzyme (MTND4) encoding gene, which causes Arg → Ser replacement. The mutation was also detected in low copy number in blood of mother. Albeit this mutation type is well recognized as a typical mtDNA mutation, according the reports available on the PubMed, this mutation was described only in four patients with wide phenotypic variations; here, we reviewed the characteristic clinical features of them. Taken together, the earliest onset of symptoms, the nature of the first presentation signs, the most rapid progression, the character of minor additional symptoms, and the early fatal outcome differentiate the phenotypic variant of the proband presented here from cases reported so far by others.

KW - Leigh syndrome

KW - Mitochondrial DNA mtDNA 11777C> A

KW - Mitochondrial mutation

UR - http://www.scopus.com/inward/record.url?scp=78649962110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649962110&partnerID=8YFLogxK

U2 - 10.1007/s12017-010-8115-9

DO - 10.1007/s12017-010-8115-9

M3 - Article

VL - 12

SP - 277

EP - 284

JO - NeuroMolecular Medicine

JF - NeuroMolecular Medicine

SN - 1535-1084

IS - 3

ER -