title: 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.
authors.affiliation: 1] Laboratoire de biochimie 'hormonologie, métabolisme-nutrition, oncologie', Centre de Biologie Pathologie, CHRU de Lille, Lille Cedex, France [2] INSERM, U837, Team 5, Lille Cedex, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Coppin
authors.affiliation: Laboratoire de biochimie 'hormonologie, métabolisme-nutrition, oncologie', Centre de Biologie Pathologie, CHRU de Lille, Lille Cedex, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Grutzmacher
authors.affiliation: Laboratoire de biochimie 'hormonologie, métabolisme-nutrition, oncologie', Centre de Biologie Pathologie, CHRU de Lille, Lille Cedex, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Crépin
authors.affiliation: Laboratoire de biochimie 'hormonologie, métabolisme-nutrition, oncologie', Centre de Biologie Pathologie, CHRU de Lille, Lille Cedex, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Destailleur
authors.affiliation: Laboratoire de génétique, Groupement Hospitalier Edouard Herriot, Lyon, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Giraud
authors.affiliation: Service d'endocrinologie et métabolismes, hôpital Claude-Huriez, CHRU de Lille, Lille Cedex, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cardot-Bauters
authors.affiliation: 1] Laboratoire de biochimie 'hormonologie, métabolisme-nutrition, oncologie', Centre de Biologie Pathologie, CHRU de Lille, Lille Cedex, France [2] INSERM, U837, Team 5, Lille Cedex, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Porchet
authors.affiliation: 1] Laboratoire de biochimie 'hormonologie, métabolisme-nutrition, oncologie', Centre de Biologie Pathologie, CHRU de Lille, Lille Cedex, France [2] INSERM, U837, Team 5, Lille Cedex, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Pigny
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D010641:Phenotype; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D006623:von Hippel-Lindau Disease / Q000175:diagnosis / Q000235:genetics*
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human