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VHL mosaicism can be detected by clinical next-generation sequencing and is not restricted to patients with a mild phenotype.

ABSTRACT: The identification of Von Hippel-Lindau (VHL) mosaic mutations by conventional Sanger sequencing requires a labour-intensive enrichment step, thus explaining that mosaicism occurrence is underestimated in patients. Nowadays, it is possible to detect mutation in cell sub-populations by next-generation sequencing (NGS). Here, we described a diagnosis strategy using NGS with high coverage in a series of eight patients who were negative for a VHL abnormality by Sanger sequencing and deletion search. In two patients, a mosaic mutation in VHL was detected by NGS. One patient with a 5.7% mutated allele frequency had a severe phenotype and an early disease onset. In conclusion, clinical NGS in an hospital molecular oncogenetics laboratory is an efficient tool to identify VHL mosaic mutation. Its use may improve patient monitoring and genetic counseling.

SUBMITTER: Coppin L

PROVIDER: S-EPMC4135403 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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VHL mosaicism can be detected by clinical next-generation sequencing and is not restricted to patients with a mild phenotype.

Coppin Lucie L Grutzmacher Claudine C Crépin Michel M Destailleur Evelyne E Giraud Sophie S Cardot-Bauters Catherine C Porchet Nicole N Pigny Pascal P

European journal of human genetics : EJHG 20131204 9

The identification of Von Hippel-Lindau (VHL) mosaic mutations by conventional Sanger sequencing requires a labour-intensive enrichment step, thus explaining that mosaicism occurrence is underestimated in patients. Nowadays, it is possible to detect mutation in cell sub-populations by next-generation sequencing (NGS). Here, we described a diagnosis strategy using NGS with high coverage in a series of eight patients who were negative for a VHL abnormality by Sanger sequencing and deletion search. ...[more]

PMID: 24301059

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Dataset Information

VHL mosaicism can be detected by clinical next-generation sequencing and is not restricted to patients with a mild phenotype.

Publications

VHL mosaicism can be detected by clinical next-generation sequencing and is not restricted to patients with a mild phenotype.

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