NF1 single and multi-exons copy number variations in neurofibromatosis type 1

被引:15
作者
Imbard, Apolline [1 ]
Pasmant, Eric [2 ,3 ]
Sabbagh, Audrey [4 ]
Luscan, Armelle [2 ,3 ]
Soares, Magali [3 ]
Goussard, Philippe [3 ]
Blanche, Helene [5 ]
Laurendeau, Ingrid [2 ]
Ferkal, Salah [6 ]
Vidaud, Michel [2 ,3 ]
Pinson, Stephane [7 ]
Bellanne-Chantelot, Christine [8 ]
Vidaud, Dominique [2 ,3 ]
Wolkenstein, Pierre [9 ,10 ]
Parfait, Beatrice [2 ,3 ]
机构
[1] Hop Robert Debre, Serv Biochim Hormonol, AP HP, F-75019 Paris, France
[2] Univ Paris 05, Sorbonne Paris Cite, Fac Sci Pharmaceut & Biol, EA7331, F-75006 Paris, France
[3] Hop Cochin, Serv Biochim & Genet Mol, AP HP, F-75674 Paris, France
[4] Univ Paris 05, Sorbonne Paris Cite, Fac Sci Pharmaceut & Biol, IRD,UMR216,Mere & Enfant Face Infect Trop, F-75006 Paris, France
[5] Fdn Jean Dausset Ctr Etud Polymorphisme Humain CE, Inst Genet Mol, Paris, France
[6] Grp Hosp Henri Mondor Albert Chenevier, INSERM, Ctr Invest Clin 006, AP HP, Creteil, France
[7] Hop Edouard Herriot, Serv Genet Mol, Lyon, France
[8] Univ Paris 06, Hop La Pitie Salpetriere, Dept Genet, AP HP, Paris, France
[9] Univ Paris Est Creteil, Dept Dermatol, Ctr Reference Neurofibromatoses, Hop Henri Mondor,AP HP, Creteil, France
[10] Univ Paris Est Creteil, EA LIC 4393, Creteil, France
关键词
RECURRENT MUTATIONS; GENE; GENOTYPE; EXPRESSION; SPECTRUM; DOMAIN;
D O I
10.1038/jhg.2015.6
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 (similar to 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.
引用
收藏
页码:221 / 224
页数:4
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