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NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype

✍ Scribed by Eric Pasmant; Audrey Sabbagh; Gill Spurlock; Ingrid Laurendeau; Elisa Grillo; Marie-José Hamel; Ludovic Martin; Sébastien Barbarot; Bruno Leheup; Diana Rodriguez; Didier Lacombe; Hélène Dollfus; Laurent Pasquier; Bertrand Isidor; Salah Ferkal; Jean Soulier; Marc Sanson; Anne Dieux-Coeslier; Ivan Bièche; Béatrice Parfait; Michel Vidaud; Pierre Wolkenstein; Meena Upadhyaya; Dominique Vidaud

Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
197 KB
Volume
31
Category
Article
ISSN
1059-7794

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✦ Synopsis

In 5-10% of patients, neurofibromatosis type 1 (NF1) results from microdeletions that encompass the entire NF1 gene and a variable number of flanking genes. Two recurrent microdeletion types are found in most cases, with microdeletion breakpoints located in paralogous regions flanking NF1 (proximal NF1-REP-a and distal NF1-REP-c for the 1.4 Mb type-1 microdeletion, and SUZ12 and SUZ12P for the 1.2 Mb type-2 microdeletion). A more severe phenotype is usually associated with NF1 microdeletion patients than in those with intragenic mutations. We characterized NF1 microdeletions in 70 unrelated NF1 microdeleted patients using a high-resolution NF1 custom array comparative genomic hybridization (CGH). Genotype-phenotype correlations were studied in 58 of these microdeletion patients and compared to 389 patients with intragenic truncating NF1 mutations and phenotyped in the same standardized way. Our results confirmed in an unbiased manner the existence of a contiguous gene syndrome with a significantly higher incidence of learning disabilities and facial dysmorphism in microdeleted patients compared to patients with intragenic NF1 mutations. Microdeleted NF1 patients also showed a trend toward significance for childhood overgrowth. High-resolution array-CGH identified a new recurrent approximately 1.0 Mb microdeletion type, designated as type-3, with breakpoints in the paralogous regions middle NF1-REP-b and distal NF1-REP-c.

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