Is there a link between COQ6 and schwannomatosis?

Trevisson, Eva; Clementi, Maurizio; Salviati, Leonardo

doi:10.1038/gim.2014.211

Cited by 6 publications

(5 citation statements)

References 3 publications

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“…Although the deleterious effects of the COQ6 missense mutation were validated by its lack of complementation in a coq6 -deficient yeast mutant, there was no evidence for either a dominant-negative effect or a toxic gain of function of the missense COQ6 variant detected; hence, the mechanism of tumorigenesis in this schwannomatosis family remains unexplained. As opined by Trevisson et al (2015), further studies are necessary to ascertain whether COQ6 might play a role in the etiology of schwannomatosis.…”

Section: Somatic Mosaicism In Schwannomatosis and Unknown Schwannomatmentioning

confidence: 94%

The molecular pathogenesis of schwannomatosis, a paradigm for the co-involvement of multiple tumour suppressor genes in tumorigenesis

et al. 2016

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Schwannomatosis is characterized by the predisposition to develop multiple schwannomas and, less commonly, meningiomas. Despite the clinical overlap with neurofibromatosis type 2 (NF2), schwannomatosis is not caused by germline NF2 gene mutations. Instead, germline mutations of either the SMARCB1 or LZTR1 tumour suppressor genes have been identified in 86% of familial and 40% of sporadic schwannomatosis patients. In contrast to patients with rhabdoid tumours, which are due to complete loss-of-function SMARCB1 mutations, individuals with schwannomatosis harbour predominantly hypomorphic SMARCB1 mutations which give rise to the synthesis of mutant proteins with residual function that do not cause rhabdoid tumours. Although biallelic mutations of SMARCB1 or LZTR1 have been detected in the tumours of patients with schwannomatosis, the classical two-hit model of tumorigenesis is insufficient to account for schwannoma growth, since NF2 is also frequently inactivated in these tumours. Consequently, tumorigenesis in schwannomatosis must involve the mutation of at least two different tumour suppressor genes, an occurrence frequently mediated by loss of heterozygosity of large parts of chromosome 22q harbouring not only SMARCB1 and LZTR1 but also NF2. Thus, schwannomatosis is paradigmatic for a tumour predisposition syndrome caused by the concomitant mutational inactivation of two or more tumour suppressor genes. This review provides an overview of current models of tumorigenesis and mutational patterns underlying schwannomatosis that will ultimately help to explain the complex clinical presentation of this rare disease.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-016-1753-8) contains supplementary material, which is available to authorized users.

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Section: Somatic Mosaicism In Schwannomatosis and Unknown Schwannomatmentioning

confidence: 94%

The molecular pathogenesis of schwannomatosis, a paradigm for the co-involvement of multiple tumour suppressor genes in tumorigenesis

et al. 2016

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“…He is now on peritoneal dialysis treatment, however, CoQ10 treatment was started to prevent neurological symptoms. Interestingly, there was no history of schwannomatosis in the patient's family, and unless further evidence supporting the link between heterozygous COQ6 mutations and schwannomatosis becomes available, we do not recommend mutational screening of COQ6 gene for schwannomas carriers (5). The most frequent glomerular lesion associated with COQ6 changes is FSGS (4).…”

mentioning

confidence: 99%

Further phenotypic heterogeneity of CoQ10 deficiency associated with steroid resistant nephrotic syndrome and novel COQ2 and COQ6 variants

et al. 2017

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“…This mutation is reported to lead to haploinsufficiency of COQ6, predisposing individuals harboring the mutation to schwannomatosis, which is a rare genetic disorder resulting in multiple benign schwannomas growing on peripheral nerves [ 96 ]. However, further studies must be conducted to confirm this link [ 97 ].…”

Section: Resultsmentioning

confidence: 99%

Predicting and Understanding the Pathology of Single Nucleotide Variants in Human COQ Genes

Wang¹,

Jain²,

Novales³

et al. 2022

Antioxidants

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Coenzyme Q (CoQ) is a vital lipid that functions as an electron carrier in the mitochondrial electron transport chain and as a membrane-soluble antioxidant. Deficiencies in CoQ lead to metabolic diseases with a wide range of clinical manifestations. There are currently few treatments that can slow or stop disease progression. Primary CoQ10 deficiency can arise from mutations in any of the COQ genes responsible for CoQ biosynthesis. While many mutations in these genes have been identified, the clinical significance of most of them remains unclear. Here we analyzed the structural and functional impact of 429 human missense single nucleotide variants (SNVs) that give rise to amino acid substitutions in the conserved and functional regions of human genes encoding a high molecular weight complex known as the CoQ synthome (or Complex Q), consisting of the COQ3–COQ7 and COQ9 gene products. Using structures of COQ polypeptides, close homologs, and AlphaFold models, we identified 115 SNVs that are potentially pathogenic. Further biochemical characterizations in model organisms such as Saccharomyces cerevisiae are required to validate the pathogenicity of the identified SNVs. Collectively, our results will provide a resource for clinicians during patient diagnosis and guide therapeutic efforts toward combating primary CoQ10 deficiency.

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Is there a link between COQ6 and schwannomatosis?

Cited by 6 publications

References 3 publications

The molecular pathogenesis of schwannomatosis, a paradigm for the co-involvement of multiple tumour suppressor genes in tumorigenesis

The molecular pathogenesis of schwannomatosis, a paradigm for the co-involvement of multiple tumour suppressor genes in tumorigenesis

Further phenotypic heterogeneity of CoQ10 deficiency associated with steroid resistant nephrotic syndrome and novel COQ2 and COQ6 variants

Predicting and Understanding the Pathology of Single Nucleotide Variants in Human COQ Genes

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