Genetic analysis of Neurofibromatosis type 1 (NF1) may facilitate the identification of patients in early phases of the disease. Here, we present an overview of our diagnostic research spanning the last eleven years, with a focus on the description of 225 NF1 mutations, 126 of which are novel, found in a series of 605 patients (513 unrelated) in Italy. Between 2003 and 2013, 443 unrelated patients were profiled by DHPLC analysis of 60 amplicons derived from genomic NF1 DNA and subsequent sequencing of heterozygotic PCR products. In addition, a subset of patients was studied by MLPA to identify any duplications, large deletions or microdeletions present at the locus. Over the last year, 70 unrelated patients were investigated by MLPA and sequencing of 22 amplicons spanning the entire NF1 cDNA. Mutations were found in 70% of the 293 patients studied by DHPLC, thereby fulfilling the NIH criterion for the clinical diagnosis of NF1 (detection rate: 70%); furthermore, 87% of the patients studied by RNA sequencing were genetically characterized. Mutations were also found in 36 of the 159 patients not fulfilling the NIH clinical criteria. These data support the use of RNA-based methods for genetic analysis and provide novel information for relevant for improving the management of symptoms in oligosymptomatic patients.

(2014). Integrated genetic diagnosis of neurofibromatosis type 1 (NF1) and molecular characterization of one case of compound heterozygosity. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2014).

Integrated genetic diagnosis of neurofibromatosis type 1 (NF1) and molecular characterization of one case of compound heterozygosity

MOROSINI, SARA
2014

Abstract

Genetic analysis of Neurofibromatosis type 1 (NF1) may facilitate the identification of patients in early phases of the disease. Here, we present an overview of our diagnostic research spanning the last eleven years, with a focus on the description of 225 NF1 mutations, 126 of which are novel, found in a series of 605 patients (513 unrelated) in Italy. Between 2003 and 2013, 443 unrelated patients were profiled by DHPLC analysis of 60 amplicons derived from genomic NF1 DNA and subsequent sequencing of heterozygotic PCR products. In addition, a subset of patients was studied by MLPA to identify any duplications, large deletions or microdeletions present at the locus. Over the last year, 70 unrelated patients were investigated by MLPA and sequencing of 22 amplicons spanning the entire NF1 cDNA. Mutations were found in 70% of the 293 patients studied by DHPLC, thereby fulfilling the NIH criterion for the clinical diagnosis of NF1 (detection rate: 70%); furthermore, 87% of the patients studied by RNA sequencing were genetically characterized. Mutations were also found in 36 of the 159 patients not fulfilling the NIH clinical criteria. These data support the use of RNA-based methods for genetic analysis and provide novel information for relevant for improving the management of symptoms in oligosymptomatic patients.
FINOCCHIARO, GAETANO
Neurofibromatosis type 1 (NF1); mutation database; novel mutations; diagnostic criteria.
BIO/11 - BIOLOGIA MOLECOLARE
English
15-lug-2014
Scuola di Dottorato in Medicina Traslazionale e Molecolare
SCUOLA DI DOTTORATO IN MEDICINA TRASLAZIONALE E MOLECOLARE (DIMET) - 72R
26
2012/2013
open
(2014). Integrated genetic diagnosis of neurofibromatosis type 1 (NF1) and molecular characterization of one case of compound heterozygosity. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2014).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/83314
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