UNCOMMON RESULTS OF NF1 MOLECULAR ANALYSIS IN A BIG FAMILY WITH NUMEROUS AFFECTED MEMBERS

PARMA DIANA; LUCE LEONELA; GILIBERTO FLORENCIA; FRANCIPANE LILIANA,; , SZIJAN IRENE; FERRER MARCELA

Mar del PLata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC) LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI) XLVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE FARMACOLOGÍA EXPERIMENTAL (SAFE); 2016

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC)

Neurofibromatosis type 1, the most common genetic disorderaffecting the human nervous system, is the result of loss-offunctionmutations of the tumor suppressor NF1 gene and inheritedin an autosomal dominant fashion. The condition predisposingindividuals to the development of neurofibromas, optic nerve gliomasand skeletal abnormalities, is fully penetrant and has a hi ghlyvariable expression, even within the same family.The molecular diagnosis of NF1 is still difficult due to the lar gesize of the gene, the existence of pseudogenes, the lack of mutationalhotspots and the complex molecular spectrum. We studiedfamilial NF1 in order to identify the family members with the riskof developing the disease. The focus was the molecular testingof the two youngest members (4 years, 2 months) of a family thatincludes 11 affected individuals out of 19 total relatives.A simple and highly sensitive methodology was used: segregationanalysis of four NF1 intragenic polymorphic microsatellites(D17S1307, D17S1849, IVS27AC28.4, IVS38GT53.0) andmutational screening using bidirectional DNA sequencing of theNF1 exons of interest. The analysis of the STRs revealed the atrisk haplotype in the 7 affected members studied and a differenthaplotype in 2 individuals who could be excluded from the risk. Theanalysis of the two probands (still unaffected children) indicatedthat one of them carries the at risk haplotype while the othercarries the different one.A recombination event was found between markers D17S1849and IVS27AC28.4 in two individuals. Interestingly one of themwas affected and the other was asymptomatic. These data suggestthat the mutation may be located between the markersmentioned above.The data obtained are important for familial genetic counsellingand allow the early diagnosis of predisposition to NF1. Thefinding of an intragenic recombination is an infrequent event inthe NF1 syndrome.