title: Thirty-nine novel neurofibromatosis 1 (NF1) gene mutations identified in Slovak patients.
abstract: We performed a complex analysis of the neurofibromatosis type 1 (NF1) gene in Slovakia based on direct cDNA sequencing supplemented by multiple ligation dependent probe amplification (MLPA) analysis. All 108 patients had café-au-lait spots, 85% had axilary and/or inguinal freckling, 61% neurofibromas, 36% Lisch nodules of the iris and 31% optic pathway glioma, 5% suffered from typical skeletal disorders, and 51% of patients had family members with NF1. In 78 of the 86 (90.7%) index patients our analysis revealed the presence of NF1 mutations, 68 of which were small changes (87.2%), including 39 (50%) novel. Among the identified mutations the most prevalent were small deletions and insertions causing frameshift (42.3%), followed by nonsense (14.1%), missense (12.8%), and typical splicing (11.5%) mutations. Type 1 NF1 deletions and intragenic deletions/duplication were identified in five cases each (6.4%). Interestingly, in five other cases nontypical splicing variants were found, whose real effect on NF1 transcript would have remained undetected if using a DNA-based method alone, thus underlying the advantage of using the cDNA-based sequencing. We show that Slovak NF1 patients have a similar repertoire of NF1 germline mutations compared to other populations, with some prevalence of small deletions/insertions and a decreased proportion of nonsense mutations.
authors.affiliation: Laboratory of Genetics, Institute of Molecular Physiology and Genetics, Bratislava, Slovakia.
authors.forename: Martina
authors.initials: M
authors.lastname: Nemethova
authors.forename: Anna
authors.initials: A
authors.lastname: Bolcekova
authors.forename: Denisa
authors.initials: D
authors.lastname: Ilencikova
authors.forename: Darina
authors.initials: D
authors.lastname: Durovcikova
authors.forename: Katarina
authors.initials: K
authors.lastname: Hlinkova
authors.forename: Anna
authors.initials: A
authors.lastname: Hlavata
authors.forename: Laszlo
authors.initials: L
authors.lastname: Kovacs
authors.forename: Ludevit
authors.initials: L
authors.lastname: Kadasi
authors.forename: Andrea
authors.initials: A
authors.lastname: Zatkova
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009456:Neurofibromatosis 1 / Q000175:diagnosis / Q000235:genetics*; D018154:Slovakia; D044465:White People / Q000235:genetics*; D055815:Young Adult
keywords: NF1; NF1mutations; Slovakia; cDNA based method; neurofibromatosis 1