Mitochondrial DNA maintenance disorders in 102 patients from different parts of Russia: Mutational spectrum and phenotypes

Bychkov, Igor; Itkis, Yulia S.; Tsygankova, Polina G.; Крылова, Т.Д.; Mikhaylova, Svetlana; Klyushnikov, S. A.; Печатникова, Н. Л.; Degtyareva, Anna; Николаева, Е. А.; Seliverstov, Yury; Kurbatov, S. V.; Дадали, Е. Л.; Rudenskaya, G. E.; Иллариошкин, С.Н.; Zakharova, Ekaterina

doi:10.1016/j.mito.2021.01.004

Cited by 10 publications

(6 citation statements)

References 35 publications

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“…Currently, there is a paucity of literature on adult-onset MM presenting with ARF and AHF. Some studies have reported a small proportion of patients, mostly children and rarely adults, showing both respiratory and cardiac dysfunction [6][7][8]. In a recent study of 21 pediatric cases of MM, 3 patients (14.3%) presented with sudden respiratory failure, and 5 showed cardiac enlargement, tricuspid incompetence, and pulmonary artery hypertension on echocardiography.…”

Section: Discussionmentioning

confidence: 99%

Reversible cardiac function and left ventricular hypertrophy in a Chinese man with mitochondrial myopathy: a case report

Wu,

Han,

Zhao

et al. 2023

BMC Cardiovasc Disord

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Background Mitochondrial myopathies (MMs) are a group of multi-system diseases caused by abnormalities in mitochondrial DNA (mtDNA) or mutations of nuclear DNA (nDNA). The diagnosis of mitochondrial myopathy (MM) is reliant on the combination of history and physical examination, muscle biopsy, histochemical studies, and next-generation sequencing. Patients with MMs have diverse clinical manifestations. In the contemporary literature, there is a paucity of reports on cardiac structure and function in this rare disease. We report a Chinese man with MM accompanied with both acute right heart failure and left ventricular hypertrophy. Case presentation A 49-year-old man presented with clinical features suggestive of MM, i.e., ophthalmoparesis, weakness of the pharyngeal and extremity muscles, and respiratory muscles which gradually progressed to respiratory insufficiency. He had a family history of mitochondrial myopathy. He had increased levels of serum creatine kinase and lactate. Muscle biopsy of left lateral thigh revealed 8% ragged red fibers (RRF) and 42% COX-negative fibers. Gene sequencing revealed a novel heterozygote TK2 variant (NM_001172644: c.584T>C, p.Leu195Pro) and another heterozygous variant (NM_004614.4:c.156+958G>A; rs1965661603) in the intron of TK2 gene. Based on these findings, we diagnosed the patient as a case of MM. Echocardiography revealed right heart enlargement, pulmonary hypertension, left ventricular hypertrophy, and thickening of the main pulmonary artery and its branches. The patient received non-invasive ventilation and coenzyme Q10 (CoQ10). The cardiac structure and function were restored at 1-month follow-up. Conclusions This is the first report of reversible cardiac function impairment and left ventricular hypertrophy in a case of adult-onset MM, nocturnal hypoxia is a potential mechanism for left ventricular hypertrophy in patients with MM.

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Section: Discussionmentioning

confidence: 99%

Reversible cardiac function and left ventricular hypertrophy in a Chinese man with mitochondrial myopathy: a case report

Wu,

Han,

Zhao

et al. 2023

BMC Cardiovasc Disord

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“…SUCLG1-related encephalomyopathy is an autosomal recessive disorder. Case with MTDPS9 are rare and about 30 SUCLG1 variants have been reported, including missense, splice site and nonsense variants (Rouzier et al, 2010;Van Hove et al, 2010;Carrozzo et al, 2016;Liu et al, 2016;Molaei et al, 2020;Bychkov et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…To date, errors in 25 nuclear genes have been identified as causes of MDS. These genes are involved in the mitochondrial deoxynucleotide triphosphate (dNTP) supply for mtDNA nucleotides metabolism ( SUCLG1 , SUCLA2 , RRM2B , TK2 , DGUOK , TYMP , ABAT , SLC25A4 , AGK , MPV17 , DTYMK ), mtDNA replisome ( POLG , POLG2 , TWNK , DNA2 , MGME1 , TFAM , RNASH1 ), mitochondrial communications ( OPA1 , OPA3 , MFN2 , FBXL4 ), protein folding and degradation ( GFER , SPG7 , AFG3L2 ) or other roles in mitochondrial maintenance ( MRM2 , SLC25A21 , SLC25A10 ) (El‐Hattab and Scaglia, 2013; Garone et al, 2017; Viscomi and Zeviani, 2017; Molaei et al, 2020; Wang et al, 2020; Bychkov et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Novel compound heterozygous SUCLG1 variants may contribute to mitochondria DNA depletion syndrome‐9

Chen

et al. 2022

Molec Gen & Gen Med

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Background Succinate‐CoA ligase/synthetase (SCS) deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Variants in SUCLG1, the nuclear gene encoding the alpha subunit of the SCS enzyme playing a pivotal role in maintaining mtDNA integrity and stability, are associated with mitochondrial DNA depletion syndrome 9 (MTDPS9). Methods In this study, we reported an infant with clinical features of MTDPS9 from China. Whole exome sequencing (WES) was used to identify the genetic cause. Bioinformatic analysis and mtDNA level detection were performed to assess pathogenicity. Results The proband manifested with hypotonia, lactic acidosis, mild methylmalonic aciduria, hearing loss and psychomotor retardation. WES identified new compound heterozygous SUCLG1 variants of c.601A>G (p.R201G) in exon 6 and c.871G>C (p.A291P) in exon 8. Computational analysis predicted that these missense variants might alter structure stability and mitochondrial translocation of SUCLG1. qRT‐PCR showed 68% depletion of mtDNA content in proband as compared to controls. Conclusion Novel compound heterozygous variants c.601A>G (p.R201G) and c.871G>C (p.A291P) in SUCLG1 may cause MTDPS9 in this family. Our finding should be helpful for molecular diagnosis, genetic counseling and clinical management of SCS deficiency disorders.

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“…Later, at the age of 8 years, a genetic test revealed a homozygous mutation in the first exon of DGUOK (c.3G>A, p.Met1Ile). This is the most common mutation leading to the hepatocerebral form of MDS and isolated liver failure in the Russian population [ 9 ]. At the age of 12 years, the patient presented with important amyotrophy and an occasional cough that became chronic.…”

Section: Case Presentationmentioning

confidence: 99%

Deoxyguanosine kinase deficiency and recurrent spontaneous pneumothorax: a case report

Ramboux,

Poncelet,

Clapuyt

et al. 2023

J Med Case Reports

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Background Deoxyguanosine kinase deficiency is mainly manifested by hepatic and neurological damage, hence it belongs to the hepatocerebral form of mitochondrial deoxyribonucleic acid depletion syndrome. The association between deoxyguanosine kinase deficiency and recurrent spontaneous pneumothorax has not currently been reported. Case presentation A 12-year-old Russian boy with deoxyguanosine kinase deficiency, a recipient of a liver transplant with amyotrophy secondary to his mitochondriopathy, presented with recurrent spontaneous bilateral pneumothorax refractory to drainage and surgery. Conclusion To our knowledge, this is the first documented case of deoxyguanosine kinase deficiency associated with recurrent spontaneous pneumothorax, which could be considered a late complication of deoxyguanosine kinase deficiency. At this point, this is only an association and further studies and research need to be performed to help confirm the pathogenesis of this association.

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Mitochondrial DNA maintenance disorders in 102 patients from different parts of Russia: Mutational spectrum and phenotypes

Cited by 10 publications

References 35 publications

Reversible cardiac function and left ventricular hypertrophy in a Chinese man with mitochondrial myopathy: a case report

Reversible cardiac function and left ventricular hypertrophy in a Chinese man with mitochondrial myopathy: a case report

Novel compound heterozygous SUCLG1 variants may contribute to mitochondria DNA depletion syndrome‐9

Deoxyguanosine kinase deficiency and recurrent spontaneous pneumothorax: a case report

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