Combined Mutation And Rearrangement Screening by Quantitative PCR High-Resolution Melting: Is It Relevant for Hereditary Recurrent Fever Genes?

Pallares-Ruiz, Nathalie; Dumont, Bruno; Fabre, Aurélie; Cuisset, Laurence; Cointin, Elodie; Rittore, Cécile; Soler, Stephan; Touitou, Isabelle

doi:10.1371/journal.pone.0014096

Cited by 5 publications

(3 citation statements)

References 18 publications

(18 reference statements)

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“…HRF sequence variants are associated with a broad range of phenotypes, but only a small proportion of them have been clearly shown to be the direct cause of the disease. The most common variants seen in the HRF genes are non-synonymous nucleotide changes and with the exception of MKD, no large structural mutations (deletions, duplications, rearrangement) have been reported 24 25. This is probably because such deleterious pathogenic variants would not be tolerated in genes that regulate host defence pathways.…”

Section: Discussionmentioning

confidence: 99%

Guidelines for the genetic diagnosis of hereditary recurrent fevers

et al. 2012

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Hereditary recurrent fevers (HRFs) are a group of monogenic autoinflammatory diseases characterised by recurrent bouts of fever and serosal inflammation that are caused by pathogenic variants in genes important for the regulation of innate immunity. Discovery of the molecular defects responsible for these diseases has initiated genetic diagnostics in many countries around the world, including the Middle East, Europe, USA, Japan and Australia. However, diverse testing methods and reporting practices are employed and there is a clear need for consensus guidelines for HRF genetic testing.Draft guidelines were prepared based on current practice deduced from previous HRF external quality assurance schemes and data from the literature. The draft document was disseminated through the European Molecular Genetics Quality Network for broader consultation and amendment. A workshop was held in Bruges (Belgium) on 18 and 19 September 2011 to ratify the draft and obtain a final consensus document. An agreed set of best practice guidelines was proposed for genetic diagnostic testing of HRFs, for reporting the genetic results and for defining their clinical significance.

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Section: Discussionmentioning

confidence: 99%

Guidelines for the genetic diagnosis of hereditary recurrent fevers

et al. 2012

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“…relative quantification, and data was normalized against an endogenous control primer that amplifies exon 11 of NLRP7, for which the two alleles are amplified based on the presence of a heterozygous SNP. For the other samples, patient 1 and her family members and patient 6, multiplex ligation-dependent probe amplification was performed, as previously described [26].…”

Section: Microarrays Analysismentioning

confidence: 99%

The genetics of recurrent hydatidiform moles: new insights and lessons from a comprehensive analysis of 113 patients

et al. 2018

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Hydatidiform mole is an aberrant human pregnancy characterized by early embryonic arrest and excessive trophoblastic proliferation. Recurrent hydatidiform moles are defined by the occurrence of at least two hydatidiform moles in the same patient. Fifty to eighty percent of patients with recurrent hydatidiform moles have biallelic pathogenic variants in NLRP7 or KHDC3L. However, in the remaining patients, the genotypic types of the moles are unknown. We characterized 80 new hydatidiform mole tissues, 57 of which were from patients with no mutations in the known genes, and we reviewed the genotypes of a total of 123 molar tissues. We also reviewed mutation analysis in 113 patients with recurrent hydatidiform moles. While all hydatidiform moles from patients with biallelic NLRP7 or KHDC3L mutations are diploid biparental, we demonstrate that those from patients without mutations are highly heterogeneous and only a small minority of them are diploid biparental (8%). The other mechanisms that were found to recur in patients without mutations are diploid androgenetic monospermic (24%) and triploid dispermic (32%); the remaining hydatidiform moles were misdiagnosed as moles due to errors in the analyses and/or their unusual mechanisms. We compared three parameters of genetic susceptibility in patients with and without mutations and show that patients without mutations are mostly from non-familial cases, have fewer reproductive losses, and more live births. Our data demonstrate that patients with recurrent hydatidiform moles and no mutations in the known genes are, in general, different from those with mutations; they have a milder genetic susceptibility and/or a multifactorial etiology underlying their recurrent hydatidiform moles. Categorizing these patients according to the genotypic types of their recurrent hydatidiform moles may facilitate the identification of novel genes for this entity.

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“…3 To specify the extent of the whole gene deletion, we used a CytoScanHD array from Affymetrix, according to the supplier's instructions. 1 incomplete penetrance* Figure 1 Workflow showing the different steps and subjects enrolled in our study.…”

Section: Rearrangement Screening By Mlpa and Quantitative Pcr Confirmmentioning

confidence: 99%

The expanding spectrum of COL2A1 gene variants IN 136 patients with a skeletal dysplasia phenotype

Barat‐Houari

Dumont²,

Fabre³

et al. 2015

Eur J Hum Genet

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Heterozygous COL2A1 variants cause a wide spectrum of skeletal dysplasia termed type II collagenopathies. We assessed the impact of this gene in our French series. A decision tree was applied to select 136 probands (71 Stickler cases, 21 Spondyloepiphyseal dysplasia congenita cases, 11 Kniest dysplasia cases, and 34 other dysplasia cases) before molecular diagnosis by Sanger sequencing. We identified 66 different variants among the 71 positive patients. Among those patients, 18 belonged to multiplex families and 53 were sporadic. Most variants (38/44, 86%) were located in the triple helical domain of the collagen chain and glycine substitutions were mainly observed in severe phenotypes, whereas arginine to cysteine changes were more often encountered in moderate phenotypes. This series of skeletal dysplasia is one of the largest reported so far, adding 44 novel variants (15%) to published data. We have confirmed that about half of our Stickler patients (46%) carried a COL2A1 variant, and that the molecular spectrum was different across the phenotypes. To further address the question of genotype-phenotype correlation, we plan to screen our patients for other candidate genes using a targeted next-generation sequencing approach.

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Combined Mutation And Rearrangement Screening by Quantitative PCR High-Resolution Melting: Is It Relevant for Hereditary Recurrent Fever Genes?

Cited by 5 publications

References 18 publications

Guidelines for the genetic diagnosis of hereditary recurrent fevers

Guidelines for the genetic diagnosis of hereditary recurrent fevers

The genetics of recurrent hydatidiform moles: new insights and lessons from a comprehensive analysis of 113 patients

The expanding spectrum of COL2A1 gene variants IN 136 patients with a skeletal dysplasia phenotype

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