The dilemma of diagnosing coenzyme Q10 deficiency in muscle

Louw, R.; Smuts, Izelle; Wilsenach, Kimmey-Li; Jonck, Lindi-Maryn; Schoonen, Maryke; Westhuizen, Francois H. van der

doi:10.1016/j.ymgme.2018.02.015

Cited by 10 publications

(8 citation statements)

References 27 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, she had CI, CIII, and CII þ CIII RC deficiency, with severely reduced CoQ 10 levels in muscle. 16 These mutations cause structural instability in electron-transferring-flavoprotein dehydrogenase (ETFDH) and were confirmed with functional analysis. 38 Likely Pathogenic Variants An African female (S085), with clinically confirmed Leigh disease (OMIM number 256000) and confirmed mitochondrial CIV deficiency, harbored compound heterozygosity for missense and frameshift variants (c.575G>A and c.754_755delAG; p.Arg192Gln and p.Ser252HisfsTer39; ENST00000371974) in exons 6 and 8, respectively, in the gene SURF1.…”

Section: Pathogenic Variantsmentioning

confidence: 88%

“…Enzymes were analyzed in 600 Â g homogenates prepared from frozen muscle samples, as previously described. 7,14 Other biochemical analyses performed included urine metabolic analysis 7,9,15 and muscle coenzyme Q 10 (CoQ 10 ) analysis 16 in muscle samples. In total, 127 patients were identified to have an RC deficiency.…”

Section: Biochemical Analysismentioning

confidence: 99%

“…An African female (S002) with confirmed primary CoQ 10 deficiency 16 was found to be carrying compound heterozygous variants (c.41G>A and c.859G>T; p.Trp14Ter and p.Ala49Ser; ENST00000394026) in the gene COQ6. One of the variants identified in a highly conserved region, c.41G>A, results in a premature truncation of the protein with high loss-of-function (LoF) probability.…”

Section: Pathogenic Variantsmentioning

confidence: 99%

See 2 more Smart Citations

Panel-Based Nuclear and Mitochondrial Next-Generation Sequencing Outcomes of an Ethnically Diverse Pediatric Patient Cohort with Mitochondrial Disease

Schoonen

Smuts

Louw

et al. 2019

The Journal of Molecular Diagnostics

Self Cite

View full text Add to dashboard Cite

CME Accreditation Statement: This activity ("JMD 2019 CME Program in Molecular Diagnostics") has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the American Society for Clinical Pathology (ASCP) and the American Society for Investigative Pathology (ASIP). ASCP is accredited by the ACCME to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity ("JMD 2019 CME Program in Molecular Diagnostics") for a maximum of 18.0 AMA PRA Category 1 Credit(s) ä . Physicians should claim only credit commensurate with the extent of their participation in the activity.

show abstract

Section: Pathogenic Variantsmentioning

confidence: 88%

Section: Biochemical Analysismentioning

confidence: 99%

Section: Pathogenic Variantsmentioning

confidence: 99%

See 1 more Smart Citation

Panel-Based Nuclear and Mitochondrial Next-Generation Sequencing Outcomes of an Ethnically Diverse Pediatric Patient Cohort with Mitochondrial Disease

Schoonen

Smuts

Louw

et al. 2019

The Journal of Molecular Diagnostics

Self Cite

View full text Add to dashboard Cite

show abstract

“…The bioinformatics pipeline for variant annotation and filtering of amplicon and exome sequencing data presented here has been successfully used in research forming part of the project 'Investigating the aetiology of South African paediatric patients diagnosed with mitochondrial disorders'. [11][12][13][14]…”

Section: Introductionmentioning

confidence: 99%

bioinformatics pipeline for rare genetic diseases in South African patients

Schoonen¹,

Seyffert²,

Westhuizen³

et al. 2019

S. Afr. J. Sci.

Self Cite

View full text Add to dashboard Cite

The research fields of bioinformatics and computational biology are growing rapidly in South Africa. Bioinformatics pipelines play an integral part in handling sequencing data, which are used to investigate the aetiology of common and rare diseases. Bioinformatics platforms for common disease aetiology are well supported and continuously being developed in South Africa. However, the same is not the case for rare diseases aetiology research. Investigations into the latter rely on international cloud-based tools for data analyses and ultimately confirmation of a genetic disease. However, these tools are not necessarily optimised for ethnically diverse population groups. We present an in-house developed bioinformatics pipeline to enable researchers to annotate and filter variants in either exome or amplicon next-generation sequencing data. This pipeline was developed using next-generation sequencing data of a predominantly African cohort of patients diagnosed with rare disease. Significance: We demonstrate the feasibility of in-country development of ethnicity-sensitive, automated bioinformatics pipelines using free software in a South African context. We provide a roadmap for development of similarly ethnicity-sensitive bioinformatics pipelines.

show abstract

“…With interest we read the article by Louw et al about measuring coenzyme-Q(CoQ)-levels in frozen muscle biopsies and work-up for the causes CoQ-deficiency.in 76 biopsies from patients with a suspected respiratory chain defect(RCD) [ 1 ]. We have the following comments and concerns.…”

mentioning

confidence: 99%