Leigh Syndrome in a Pedigree Harboring the m.1555A&gt;G Mutation in the Mitochondrial 12S rRNA

Habbane, Mouna; Llobet, Laura; Bayona‐Bafaluy, M. Pilar; Bárcena, José Eulalio; Ceberio, Leticia; Gómez-Díaz, Covadonga; Gort, Laura; Artuch, Rafael; Montoya, Julio; Ruiz‐Pesini, Eduardo

doi:10.3390/genes11091007

Cited by 6 publications

(4 citation statements)

References 32 publications

(34 reference statements)

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“…Furthermore, analysis revealed two variants m.508A>G and m.15948 A>G which is not reported on either the PhyloTree build 17 or Mitomaster for that group; the m.15948 in MT-TT is a conventional tRNA in the acceptor stem domain of threonine and the transition of A to G is considered possibly benign (29.90%) by MitoTIP. Our results are in line with other previous reported Leigh pedigrees that have showed more preference for subclades of haplogroup H; for example, H1r1 in Spanish pedigree harbouring the LS m.1555A>G Mutation in MT-RNR1 [104], and an Indian Leigh case study harbouring m.8993T>C mutation in the MT-ATP6 gene, which was found defining SNP for haplogroup H [105]. Haplogroup heterogeneity for Leigh syndrome has been reported in association with different Leigh-causing mutations; for instance, H13 has been found in association with MILS ATP6 mutant cell lines.…”

Section: Discussionsupporting

confidence: 93%

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

et al. 2021

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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 MT-TL1 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 MT-ATP6 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.

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Section: Discussionsupporting

confidence: 93%

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

et al. 2021

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“…The mutations m.1555A > G and m.1494C > T have been found in multiple independent studies and are the best-characterized mtDNA mutations associated with aminoglycoside-induced and non-syndromic deafness [ 100 , 101 , 102 ]. Atypical clinical presentations of the m.1555A mutation have also been reported in individual pedigrees affected by hearing loss and cardiomyopathy or Leigh syndrome [ 103 , 104 ]. Both 1555 and 1494 bases are located in the highly conserved decoding region of the 12S rRNA in apposition to each other but do not form a base pair.…”

Section: Mitoribosome Biogenesis and Diseasementioning

confidence: 99%

Human Mitoribosome Biogenesis and Its Emerging Links to Disease

Sanchez

Krüger

Shiriaev

et al. 2021

IJMS

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Mammalian mitochondrial ribosomes (mitoribosomes) synthesize a small subset of proteins, which are essential components of the oxidative phosphorylation machinery. Therefore, their function is of fundamental importance to cellular metabolism. The assembly of mitoribosomes is a complex process that progresses through numerous maturation and protein-binding events coordinated by the actions of several assembly factors. Dysregulation of mitoribosome production is increasingly recognized as a contributor to metabolic and neurodegenerative diseases. In recent years, mutations in multiple components of the mitoribosome assembly machinery have been associated with a range of human pathologies, highlighting their importance to cell function and health. Here, we provide a review of our current understanding of mitoribosome biogenesis, highlighting the key factors involved in this process and the growing number of mutations in genes encoding mitoribosomal RNAs, proteins, and assembly factors that lead to human disease.

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“…Mitochondrial disease is not complicated by inner ear deformity and auditory nerve dysplasia, and it causes mostly post-lingual deafness in adults [ 51 ]. The number of cochlear spiral ganglion cells in patients with the common mtDNA A1555G mutation remains significant, and the effect of cochlear implantation mainly depends on the residual number of the spiral ganglion and the integrity of the auditory nerve [ 52 ]. Doerfer et al [ 53 ] reported the postoperative effects of 25patients with mitochondrial deafness implanted with cochlear implants, all of which had severe SNHL.…”

Section: Discussionmentioning

confidence: 99%

ENT characteristics and therapeutic results in multisystemic disorders of mitochondrial encephalomyopathy

et al. 2022

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Here we report the evaluation of the frequency of subjective and objective otolaryngologic findings and therapeutic results in 32 patients with mitochondrial encephalomyopathy (MEM) from September 2001 to June 2021. Our analysis included studying the patients’ family histories, the clinical manifestations of MEM, and the therapeutic effects of treatments. The patients’ ages ranged from 2 to 77 years, with a median age of 12.3 years. We found that MEM ENT symptoms were characterized by hearing loss, dysphagia, and facial weakness. Most cases of sensorineural hearing loss were bilateral symmetrical progressive or sudden deafness since adolescence, which were often underestimated. Associated neuromuscular symptoms required mtDNA testing. Dysphagia and facial weakness occurred preferentially in middle-aged patients, and muscle biopsies were advised. Distortion product otoacoustic emissions and auditory brainstem responsetesting were more sensitive and reliable than pure tone averages for objective monitoring of pathogenesis. Administration of the mitochondrial synthase complex benefited patients with acute episodes. If patients did not fully recover and exhibitedresidual language deficits, hearing aids or cochlear implants were recommended. Counsel was given regarding synthetical treatments for facial weakness, endoscopic circopharyngealmyotomy for dysphagia, and surgical correction of ptosis. This study demonstrates that increased awareness of these symptoms is important to address appropriate interventions and avoid complications such as ablepsia, aphasia, social isolation, malnutrition, aspiration pneumonia, and heart failure in the setting of MEM.

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Leigh Syndrome in a Pedigree Harboring the m.1555A>G Mutation in the Mitochondrial 12S rRNA

Cited by 6 publications

References 32 publications

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

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

Human Mitoribosome Biogenesis and Its Emerging Links to Disease

ENT characteristics and therapeutic results in multisystemic disorders of mitochondrial encephalomyopathy

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