Five novel SUCLG1 mutations in three Chinese patients with succinate-CoA ligase deficiency noticed by mild methylmalonic aciduria

Liu, Yupeng; Li, Xiyuan; Wang, Qiao; Yuan, Ding; Song, Jinqing; Yang, Yanling

doi:10.1016/j.braindev.2015.05.002

Cited by 10 publications

(8 citation statements)

References 24 publications

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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%

“…Mitochondrial DNA depletion syndrome 9 (MTDPS9) is caused by biallelic SUCLG1 variants. Patients with SUCLG1 ‐related MDS is characterized by encephalomyopathy with mtDNA depletion (Van Hove et al, 2010 ; Liu et al, 2016 ; Molaei et al, 2020 ). Symptoms include pronounced developmental delay/cognitive impairment, growth retardation, feeding difficulty, failure to thrive, hepatopathy, sensorineural hearing loss, and dystonia.…”

Section: Introductionmentioning

confidence: 99%

“…Symptoms include pronounced developmental delay/cognitive impairment, growth retardation, feeding difficulty, failure to thrive, hepatopathy, sensorineural hearing loss, and dystonia. Biochemical findings are mild methylmalonic aciduria and severe lactic acidosis (Liu et al, 2016 ). Life expectancy is usually short, with median survival of 20 months (Carrozzo et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…The mtDNA content of the patient was also decreased, accompanied by progressive myopathies. Gene sequence analysis demonstrated a homozygous mutation [c.40A>T (p.M14L)] in SUCLG1 gene ( 105 ). Clinical data showed that succinate ligase deficiency was associated with mtDNA depletion.…”

Section: Mds and Its Association With Cardiac Diseasementioning

confidence: 99%

Mitochondrial DNA Depletion Syndrome and Its Associated Cardiac Disease

Wang

Han

et al. 2022

Front. Cardiovasc. Med.

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Mitochondria is a ubiquitous, energy-supplying (ATP-based) organelle found in nearly all eukaryotes. It acts as a “power plant” by producing ATP through oxidative phosphorylation, providing energy for the cell. The bioenergetic functions of mitochondria are regulated by nuclear genes (nDNA). Mitochondrial DNA (mtDNA) and respiratory enzymes lose normal structure and function when nuclear genes encoding the related mitochondrial factors are impaired, resulting in deficiency in energy production. Massive generation of reactive oxygen species and calcium overload are common causes of mitochondrial diseases. The mitochondrial depletion syndrome (MDS) is associated with the mutations of mitochondrial genes in the nucleus. It is a heterogeneous group of progressive disorders characterized by the low mtDNA copy number. TK2, FBXL4, TYPM, and AGK are genes known to be related to MDS. More recent studies identified new mutation loci associated with this disease. Herein, we first summarize the structure and function of mitochondria, and then discuss the characteristics of various types of MDS and its association with cardiac diseases.

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“…One patient had the c.826-2A > G variant in SUCLG1 gene in a homozygous state, which had been reported to be harmful [50].…”

Section: Prenatal Diagnosis and Follow-upmentioning

confidence: 99%

The genotype analysis and prenatal genetic diagnosis among 244 pedigrees with methylmalonic aciduria in China

Liu

Jiao

et al. 2021

Preprint

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To investigate the phenotypes, biochemical features and genotypes for 244 pedigrees with methylmalonic aciduria (MMA) in China, and to perform the prenatal genetic diagnosis by chorionic villus for these pedigrees. Gene analyses were performed for 244 pedigrees. There are 130 families, chorionic villus sampling was performed on the pregnant women to conduct the prenatal diagnosis. Among 244 patients, 168 (68.9%) cases were combined methylmalonic aciduria and homocystinuria, 76 (31.1%) cases were isolated methymalonic aciduria. All the patients were diagnosed with MMA by their clinical manifestation, elevated blood propionylcarnitine, propionylcarnitine to acetylcarnitine ratio, and/or urine/blood methylmalonic acid with or without hyperhomocysteinemia. MMACHC, MUT, SUCLG1 and LMBRD1 gene variants were found in 236 (96.7%) pedigrees included 6 probands with only one heterozygous variant out of 244 cases. For the 130 pedigrees who received a prenatal diagnosis, 22 foetuses were normal, 69 foetuses were carriers of heterozygous variants, and the remaining 39 foetuses harboured compound heterozygous variants or homozygous variants. The follow-up results were consistent with the prenatal diagnosis. The present study indicates genetic heterogeneity in MMA patients. Genetic analysis is a convenient method for prenatal diagnosis that will aid in avoiding the delivery of MMA patients.

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Five novel SUCLG1 mutations in three Chinese patients with succinate-CoA ligase deficiency noticed by mild methylmalonic aciduria

Cited by 10 publications

References 24 publications

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

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

Mitochondrial DNA Depletion Syndrome and Its Associated Cardiac Disease

The genotype analysis and prenatal genetic diagnosis among 244 pedigrees with methylmalonic aciduria in China

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