Genes, Vol. 15, Pages 500: Biallelic NDUFA4 Deletion Causes Mitochondrial Complex IV Deficiency in a Patient with Leigh Syndrome
Eirik Frengen
Oxidative phosphorylation involves a complex multi-enzymatic mitochondrial machinery critical for proper functioning of the cell, and defects herein cause a wide range of diseases called “primary mitochondrial disorders” (PMDs). Mutations in about 400 nuclear and 37 mitochondrial genes have been documented to cause PMDs, which have an estimated birth prevalence of 1:5000. Here, we describe a 4-year-old female presenting from early childhood with psychomotor delay and white matter signal changes affecting several brain regions, including the brainstem, in addition to lactic and...
Source: Genes - April 17, 2024 Category: Genetics & Stem Cells Authors: Doriana Misceo Petter Str ømme Fatemeh Bitarafan Maninder Singh Chawla Ying Sheng Sandra Monica Bach de Courtade Lars Eide Eirik Frengen Tags: Article Source Type: research
Generation of a human induced pluripotent stem cell line NTUHi004-A from a patient with Leigh syndrome harboring a homozygous missense mutation c.836 T > G (p.Met279Arg) in NDUFAF5 gene
Stem Cell Res. 2024 Mar 5;76:103379. doi: 10.1016/j.scr.2024.103379. Online ahead of print.ABSTRACTLeigh syndrome is a rare autosomal recessive disorder showcasing a diverse range of neurological symptoms. Classical Leigh syndrome is associated with mitochondrial complex I deficiency, primarily resulting from biallelic mutations in the NDUFAF5 gene, encoding the NADH:ubiquinone oxidoreductase complex assembly factor 5. Using the Sendai virus delivery system, we generated an induced pluripotent stem cell line from peripheral blood mononuclear cells of a 47-years-old female patient who carried a homozygous NDUFAF5 c.836 T &g...
Source: Cell Research - March 8, 2024 Category: Cytology Authors: Chih-Hsin Ou-Yang Pin-Shiuan Chen Chin-Hsien Lin Source Type: research
Leigh syndrome with developmental regression and ataxia due to a novel splicing variant in the PMPCB gene
We report the first splice site variant in thePMPCB gene in a 39-year old individual who experienced developmental regression and ataxia following otitis media in childhood. A minigene assay confirms this variant results in aberrant splicing and skipping of exon 12. (Source: Journal of Human Genetics)
Source: Journal of Human Genetics - February 19, 2024 Category: Genetics & Stem Cells Source Type: research
Molecular and in silico investigation of a novel ECHS1 gene mutation in a consanguine family with short-chain enoyl-CoA hydratase deficiency and Mt-DNA depletion: effect on trimer assembly and catalytic activity
AbstractShort-chain enoyl-CoA hydratase deficiency (ECHS1D) is a rare congenital metabolic disorder that follows an autosomal recessive inheritance pattern. It is caused by mutations in theECHS1 gene, which encodes a mitochondrial enzyme involved in the second step of mitochondrial β-oxidation of fatty acids. The main characteristics of the disease are severe developmental delay, regression, seizures, neurodegeneration, high blood lactate, and a brain MRI pattern consistent with Leigh syndrome. Here, we report three patients belonging to a consanguineous family who presented with mitochondrial encephalomyopathy. Whole-exo...
Source: Metabolic Brain Disease - February 16, 2024 Category: Neurology Source Type: research
Impact of dietary ketosis on volatile anesthesia toxicity in a model of Leigh syndrome
CONCLUSIONS: Our findings suggest that extra caution should be taken in the anesthetic management of mitochondrial disease patients in dietary ketosis.PMID:38358320 | DOI:10.1111/pan.14855 (Source: Paediatric Anaesthesia)
Source: Paediatric Anaesthesia - February 15, 2024 Category: Anesthesiology Authors: Kira A Spencer Miranda N Howe Michael T Mulholland Vivian Truong Ryan W Liao Yihan Chen Monyreak Setha John C Snell Allison Hanaford Katerina James Philip G Morgan Margaret M Sedensky Simon C Johnson Source Type: research
Novel NARS2 variants in a patient with early-onset status epilepticus: case study and literature review
NARS2 as a member of aminoacyl-tRNA synthetases was necessary to covalently join a specific tRNA to its cognate amino acid. Biallelic variants in NARS2 were reported with disorders such as Leigh syndrome, deafnes... (Source: BMC Pediatrics)
Source: BMC Pediatrics - February 3, 2024 Category: Pediatrics Authors: Nuo Yang, Limin Chen, Yanfeng Zhang, Xuemei Wu, Yunpeng Hao, Fan Yang, Zuozhen Yang and Jianmin Liang Tags: Case Report Source Type: research
Biallelic variants in HTRA2 cause 3-methylglutaconic aciduria mitochondrial disorder: case report and literature review
Conclusion: Our findings ended the diagnostic odyssey for this family and provide further insights into the genetic and clinical spectrum of this critically under-studied disorder. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - January 18, 2024 Category: Genetics & Stem Cells Source Type: research
Interleukin-6-elicited chronic neuroinflammation may decrease survival but is not sufficient to drive disease progression in a mouse model of Leigh syndrome
Mitochondrial diseases (MDs) are genetic disorders characterized by dysfunctions in mitochondria. Clinical data suggest that additional factors, beyond genetics, contribute to the onset and progression of this... (Source: Journal of Inflammation)
Source: Journal of Inflammation - January 11, 2024 Category: Allergy & Immunology Authors: Kevin Aguilar, Carla Canal, Gemma Comes, Sandra D íaz-Clavero, Maria Angeles Llanos, Albert Quintana, Elisenda Sanz and Juan Hidalgo Tags: Research Source Type: research
GSE221586 Differential gene expression among HEK293T WT, LRPPRC-KO, LRPPRC-KO + WT, and LRPPRC-KO + Leigh Syndrome French Canadian type LRPPRC
Contributors : Antoni Barrientos ; Flavia Fontanesi ; J C Moran ; Stirling L Churchman ; Iliana Soto ; Mary T CouvillionSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Homo sapiensTo investigate the role of LRPPRC and mutant LRPPRC on the stability of the mitochondrially encoded mRNA transcripts. (Source: GEO: Gene Expression Omnibus)
Source: GEO: Gene Expression Omnibus - December 22, 2023 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Other Homo sapiens Source Type: research
Challenges in Genetic Diagnosis of Mitochondrial Diseases: What Can Functional Genomics' Studies Do?
CONCLUSION: If specific functional results are similar to controls, one might inquire about the pathogenicity of the studied variant and more genetic or bioinformatics analyses and family investigations are needed. There are also limitations of NGS in mutation detection that Sanger sequencing can overcome (P1). When performed first, the OXPHOS activity may guide to genetic screening or interpretation, concordant to later assembly results. All cases were solved and data may be crucial for genetic counseling.PMID:38111113 | DOI:10.2174/0118715303273290231211062420 (Source: Endocrine, Metabolic and Immune Disorders Drug Targets)
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - December 19, 2023 Category: Endocrinology Authors: Marta Sim ões Maria Jo ão Santos Sara Martins Maria do Carmo Mac ário Jo ão Durães Lu ísa Diogo Jo ão Paulo Oliveira Jos é Carlos Ferreira Manuela Grazina Source Type: research
Challenges in Genetic Diagnosis of Mitochondrial Diseases: What Can Functional Genomics' Studies Do?
CONCLUSION: If specific functional results are similar to controls, one might inquire about the pathogenicity of the studied variant and more genetic or bioinformatics analyses and family investigations are needed. There are also limitations of NGS in mutation detection that Sanger sequencing can overcome (P1). When performed first, the OXPHOS activity may guide to genetic screening or interpretation, concordant to later assembly results. All cases were solved and data may be crucial for genetic counseling.PMID:38111113 | DOI:10.2174/0118715303273290231211062420 (Source: Endocrine, Metabolic and Immune Disorders Drug Targets)
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - December 19, 2023 Category: Drugs & Pharmacology Authors: Marta Sim ões Maria Jo ão Santos Sara Martins Maria do Carmo Mac ário Jo ão Durães Lu ísa Diogo Jo ão Paulo Oliveira Jos é Carlos Ferreira Manuela Grazina Source Type: research
Challenges in Genetic Diagnosis of Mitochondrial Diseases: What Can Functional Genomics' Studies Do?
CONCLUSION: If specific functional results are similar to controls, one might inquire about the pathogenicity of the studied variant and more genetic or bioinformatics analyses and family investigations are needed. There are also limitations of NGS in mutation detection that Sanger sequencing can overcome (P1). When performed first, the OXPHOS activity may guide to genetic screening or interpretation, concordant to later assembly results. All cases were solved and data may be crucial for genetic counseling.PMID:38111113 | DOI:10.2174/0118715303273290231211062420 (Source: Endocrine, Metabolic and Immune Disorders Drug Targets)
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - December 19, 2023 Category: Endocrinology Authors: Marta Sim ões Maria Jo ão Santos Sara Martins Maria do Carmo Mac ário Jo ão Durães Lu ísa Diogo Jo ão Paulo Oliveira Jos é Carlos Ferreira Manuela Grazina Source Type: research
Challenges in Genetic Diagnosis of Mitochondrial Diseases: What Can Functional Genomics' Studies Do?
CONCLUSION: If specific functional results are similar to controls, one might inquire about the pathogenicity of the studied variant and more genetic or bioinformatics analyses and family investigations are needed. There are also limitations of NGS in mutation detection that Sanger sequencing can overcome (P1). When performed first, the OXPHOS activity may guide to genetic screening or interpretation, concordant to later assembly results. All cases were solved and data may be crucial for genetic counseling.PMID:38111113 | DOI:10.2174/0118715303273290231211062420 (Source: Endocrine, Metabolic and Immune Disorders Drug Targets)
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - December 19, 2023 Category: Drugs & Pharmacology Authors: Marta Sim ões Maria Jo ão Santos Sara Martins Maria do Carmo Mac ário Jo ão Durães Lu ísa Diogo Jo ão Paulo Oliveira Jos é Carlos Ferreira Manuela Grazina Source Type: research
Challenges in Genetic Diagnosis of Mitochondrial Diseases: What Can Functional Genomics' Studies Do?
CONCLUSION: If specific functional results are similar to controls, one might inquire about the pathogenicity of the studied variant and more genetic or bioinformatics analyses and family investigations are needed. There are also limitations of NGS in mutation detection that Sanger sequencing can overcome (P1). When performed first, the OXPHOS activity may guide to genetic screening or interpretation, concordant to later assembly results. All cases were solved and data may be crucial for genetic counseling.PMID:38111113 | DOI:10.2174/0118715303273290231211062420 (Source: Endocrine, Metabolic and Immune Disorders Drug Targets)
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - December 19, 2023 Category: Endocrinology Authors: Marta Sim ões Maria Jo ão Santos Sara Martins Maria do Carmo Mac ário Jo ão Durães Lu ísa Diogo Jo ão Paulo Oliveira Jos é Carlos Ferreira Manuela Grazina Source Type: research
