An Infant With a Mitochondrial A3243G Mutation Demonstrating the MELAS Phenotype

Kanaumi, Takeshi; Hirose, Shinichi; Goto, Yu‐ichi; Naitou, Etsuo; Mitsudome, Akihisa

doi:10.1016/j.pediatrneurol.2005.08.024

Cited by 16 publications

(11 citation statements)

References 12 publications

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“…Secondly, none of the T2DM patients in our study exhibit severe clinical characteristics, such as acute deafness, obesity, and stroke-like syndrome, that are often seen in MIDD and MELAS patient (Porte & Sherwin 1997;Zhong et al 2000;Chen et al 2004;Kanaumi et al 2006). Previous studies have linked Vol.…”

Section: Discussionmentioning

confidence: 71%

Mutation of mtDNA ND1 Gene in 20 Type 2 Diabetes Mellitus Patients of Gorontalonese and Javanese Ethnicity

Ishak

Puspitaningrum

Utari

et al. 2014

HAYATI Journal of Biosciences

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Mitochondrial gene mutation plays a role in the development of type two diabetes mellitus (T2DM). A point mutation in the mitochondrial gene Nicotinamide adenine dinucleotide dehydrogenase 1 (mtDNA ND1) gene mainly reported as the most common mutation related to T2DM. However, several studies have identified another SNP (singlenucleotide polymorphisms) in the RNA region of mtDNA from patients from specific ethnic populations in Indonesia. Building on those findings, this study aimed to use PCR and DNA sequencing technology to identify nucleotides in RNA and ND1 fragment from 20 Gorontalonese and 20 Javanese T2DM patients, that may trigger T2DM expression. The results showed successful amplification of RNA along 294 bp for all samples. From these samples, we found two types of point mutation in Javanese patients in the G3316A and T3200C points of the rRNA and ND1 gene. In samples taken from Gorontalonese patients, no mutation were found in the RNA or ND1 region. We conclude that T2DM was triggered differently in our two populations. While genetic mutation is implicated for the 20 Javanese patients, T2DM pathogenesis in the Gorontalonese patients must be traced to other genetic, environmental, or behavioral factors.

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Section: Discussionmentioning

confidence: 71%

Mutation of mtDNA ND1 Gene in 20 Type 2 Diabetes Mellitus Patients of Gorontalonese and Javanese Ethnicity

Ishak

Puspitaningrum

Utari

et al. 2014

HAYATI Journal of Biosciences

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“…9,28,33,[35][36][37][38][39][40][41] For example, patients with the MELAS A3243G gene mutation can present with later adult-onset deafness and diabetes or fatal encephalomyopathy with seizures and stroke-like episodes in infancy. 42 Less than 10% of patients with genetically confirmed MELAS present before the age of 1, whereas 60%-80% are diagnosed by the age of 15. There are rare case reports in the literature of patients presenting and being diagnosed as old as 80 years of age.…”

Section: Clinical Presentationmentioning

confidence: 99%

Metabolic Myopathies: Update 2009

Adel¹,

Tarnopolsky²

2009

Journal of Clinical Neuromuscular Disease

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Metabolic myopathies are inborn errors of metabolism that result in impaired energy production due to defects in glycogen, lipid, mitochondrial, and possibly adenine nucleotide metabolism. Fatty acid oxidation defects (FAOD), glycogen storage disease, and mitochondrial myopathies represent the 3 main groups of disorders, and some consider myoadenylate deaminase (AMPD1 deficiency) to be a metabolic myopathy. Clinically, a variety of neuromuscular presentations are seen at different ages of life. Newborns and infants commonly present with hypotonia and multisystem involvement (liver and brain), whereas onset later in life usually presents with exercise intolerance with or without progressive muscle weakness and myoglobinuria. In general, the glycogen storage diseases result in high-intensity exercise intolerance, whereas the FAODs and the mitochondrial myopathies manifest predominately during endurance-type activity or under fasted or other metabolically stressful conditions. The clinical examination is often normal, and testing requires various combinations of exercise stress testing, serum creatine kinase activity and lactate concentration determination, urine organic acids, muscle biopsy, neuroimaging, and specific genetic testing for the diagnosis of a specific metabolic myopathy. Prenatal screening is available in many countries for several of the FAODs through liquid chromatography-tandem mass spectrometry. Early identification of these conditions with lifestyle measures, nutritional intervention, and cofactor treatment is important to prevent or delay the onset of muscle weakness and to avoid potential life-threatening complications such as rhabdomyolysis with resultant renal failure or hepatic failure. This article will review the key clinical features, diagnostic tests, and treatment recommendations for the more common metabolic myopathies, with an emphasis on mitochondrial myopathies.

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“…The mutation load (cellular content of the A3243G mutation) is dependent on the investigated tissue. It is usually higher in muscle (up to 92%) (38–42) than in hair follicles or hair rods (35%) and higher in hair follicles than in blood lymphocytes (43–45). Individual hair roots differ markedly from one another in this respect (39).…”

Section: Mutation Load and Polymorphismsmentioning

confidence: 99%

“…The latter can be either well‐defined clinical syndromes, such as MELAS syndrome (3, 42, 67–69), MERRF syndrome (42, 67, 70), MELAS/MERRF overlap syndrome (71), chronic external ophthalmoplegia (CPEO) (4, 42, 67, 69), Kearns‐Sayre syndrome (KSS) (67–69), maternally inherited diabetes and deafness (MIDD) (42, 52, 69, 72–74), Leigh syndrome (LS) (42, 67, 75), or non‐syndromic mitochondrial disorders [floppy infant (68), enteromyopathy (68), hypertrophic cardiomyopathy (76), cluster headache (77), pancreatitis (78), renal failure (79)]. Onset of syndromic and non‐syndromic manifestations of the A3243G mutation is highly variable, ranging from early infancy to late adulthood (38, 47). The progression of A3243G mutants is worse than that of A8344G mutants and worsens with the frequency of seizures and SLEs (41).…”

Section: Phenotype Of A3243g Mutantsmentioning

confidence: 99%

Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation

Finsterer

2007

Acta Neurol Scand

104

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Mitochondrial disorders are frequently caused by mutations in mitochondrial genes and usually present as multisystem disease. One of the most frequent mitochondrial mutations is the A3,243G transition in the tRNALeu(UUR) gene. The phenotypic expression of the mutation is variable and comprises syndromic or non-syndromic mitochondrial disorders. Among the syndromic manifestations the mitochondrial encephalopathy, lactacidosis, and stroke-like episode (MELAS) syndrome is the most frequent. In single cases the A3,243G mutation may be associated with maternally inherited diabetes and deafness syndrome, myoclonic epilepsy and ragged-red fibers (MERRF) syndrome, MELAS/MERRF overlap syndrome, maternally inherited Leigh syndrome, chronic external ophthalmoplegia, or Kearns-Sayre syndrome. The wide phenotypic variability of the mutation is explained by the peculiarities of the mitochondrial DNA, such as heteroplasmy and mitotic segregation, resulting in different mutation loads in different tissues and family members. Moreover, there is some evidence that additional mtDNA sequence variations (polymorphisms, haplotypes) influence the phenotype of the A3,243G mutation. This review aims to give an overview on the actual knowledge about the genetic, pathogenetic, and phenotypic implications of the A3,243G mtDNA mutation.

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An Infant With a Mitochondrial A3243G Mutation Demonstrating the MELAS Phenotype

Cited by 16 publications

References 12 publications

Mutation of mtDNA ND1 Gene in 20 Type 2 Diabetes Mellitus Patients of Gorontalonese and Javanese Ethnicity

Mutation of mtDNA ND1 Gene in 20 Type 2 Diabetes Mellitus Patients of Gorontalonese and Javanese Ethnicity

Metabolic Myopathies: Update 2009

Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation

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