title: NF1 single and multi-exons copy number variations in neurofibromatosis type 1.
abstract: Neurofibromatosis type 1 (NF1) is caused by dominant loss-of-function mutations of the tumor suppressor NF1 containing 57 constitutive coding exons. A huge number of different pathogenic NF1 alterations has been reported. The aim of the present study was to evaluate the usefulness of a multiplex ligation-dependent probe amplification (MLPA) approach in NF1 patients to detect single and multi-exon NF1 gene copy number variations. A genotype-phenotype correlation was then performed in NF1 patients carrying these types of genetic alterations. Among 565 NF1 index cases from the French NF1 cohort, single and multi-exon deletions/duplications screening identified NF1 partial deletions/duplications in 22 patients (~4%) using MLPA analysis. Eight single exon deletions, 11 multiple exons deletions, 1 complex rearrangement and 2 duplications were identified. All results were confirmed using a custom array-CGH. MLPA and custom array-CGH allowed the identification of rearrangements that were missed by cDNA/DNA sequencing or microsatellite analysis. We then performed a targeted next-generation sequencing of NF1 that allowed confirmation of all 22 rearrangements. No clear genotype-phenotype correlations were found for the most clinically significant disease features of NF1 in patients with single and multi-exons NF1 gene copy number changes.
authors: Service de Biochimie-Hormonologie, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors: Apolline
authors: A
authors: Imbard
authors: 1] EA7331, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France [2] Service de Biochimie et de Génétique Moléculaire, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors: Eric
authors: E
authors: Pasmant
authors: IRD, UMR216, Mère et enfant face aux infections tropicales, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors: Audrey
authors: A
authors: Sabbagh
authors: 1] EA7331, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France [2] Service de Biochimie et de Génétique Moléculaire, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors: Armelle
authors: A
authors: Luscan
authors: Service de Biochimie et de Génétique Moléculaire, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors: Magali
authors: M
authors: Soares
authors: Service de Biochimie et de Génétique Moléculaire, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors: Philippe
authors: P
authors: Goussard
authors: Fondation Jean-Dausset-Centre d'Etude du Polymorphisme Humain (CEPH), Institut de Génétique Moléculaire, Paris, France.
authors: Hélène
authors: H
authors: Blanché
authors: EA7331, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors: Ingrid
authors: I
authors: Laurendeau
authors: INSERM, Centre d'Investigation Clinique 006, AP-HP, Groupe hospitalier Henri Mondor-Albert Chenevier, Créteil, France.
authors: Salah
authors: S
authors: Ferkal
authors: 1] EA7331, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France [2] Service de Biochimie et de Génétique Moléculaire, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors: Michel
authors: M
authors: Vidaud
authors: Service de Génétique Moléculaire, Hôpital Edouard-Herriot, Lyon, France.
authors: Stéphane
authors: S
authors: Pinson
authors: Département de Génétique, Hôpital de la Pitié-Salpêtrière, Université Pierre et Marie Curie, AP-HP, Paris, France.
authors: Christine
authors: C
authors: Bellanne-Chantelot
authors: 1] EA7331, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France [2] Service de Biochimie et de Génétique Moléculaire, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors: Dominique
authors: D
authors: Vidaud
authors: Département de Dermatologie, Centre de référence des neurofibromatoses, Hôpital Henri-Mondor, AP-HP and EA 4393 LIC, Université Paris Est Créteil (UPEC), Créteil, France.
authors: Pierre
authors: P
authors: Wolkenstein
authors: 1] EA7331, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France [2] Service de Biochimie et de Génétique Moléculaire, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors: Béatrice
authors: B
authors: Parfait
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005091:Exons; D005260:Female; D023061:Gene Order; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009456:Neurofibromatosis 1 / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
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