TY - JOUR
T1 - P.Arg1809Cys substitution in neurofibromin is associated with a distinctive NF1 phenotype without neurofibromas
AU - Pinna, Valentina
AU - Lanari, Valentina
AU - Daniele, Paola
AU - Consoli, Federica
AU - Agolini, Emanuele
AU - Margiotti, Katia
AU - Bottillo, Irene
AU - Torrente, Isabella
AU - Bruselles, Alessandro
AU - Fusilli, Caterina
AU - Ficcadenti, Anna
AU - Bargiacchi, Sara
AU - Trevisson, Eva
AU - Forzan, Monica
AU - Giustini, Sandra
AU - Leoni, Chiara
AU - Zampino, Giuseppe
AU - Cristina Digilio, Maria
AU - Dallapiccola, Bruno
AU - Clementi, Maurizio
AU - Tartaglia, Marco
AU - De Luca, Alessandro
PY - 2015/8/21
Y1 - 2015/8/21
N2 - Analysis of 786 NF1 mutation-positive subjects with clinical diagnosis of neurofibromatosis type 1 (NF1) allowed to identify the heterozygous c.5425C>T missense variant (p.Arg1809Cys) in six (0.7%) unrelated probands (three familial and three sporadic cases), all exhibiting a mild form of disease. Detailed clinical characterization of these subjects and other eight affected relatives showed that all individuals had multiple cafè-au-lait spots, frequently associated with skinfold freckling, but absence of discrete cutaneous or plexiform neurofibromas, Lisch nodules, typical NF1 osseous lesions or symptomatic optic gliomas. Facial features in half of the individuals were suggestive of Noonan syndrome. Our finding and revision of the literature consistently indicate that the c.5425C>T change is associated with a distinctive, mild form of NF1, providing new data with direct impact on genetic counseling and patient management.
AB - Analysis of 786 NF1 mutation-positive subjects with clinical diagnosis of neurofibromatosis type 1 (NF1) allowed to identify the heterozygous c.5425C>T missense variant (p.Arg1809Cys) in six (0.7%) unrelated probands (three familial and three sporadic cases), all exhibiting a mild form of disease. Detailed clinical characterization of these subjects and other eight affected relatives showed that all individuals had multiple cafè-au-lait spots, frequently associated with skinfold freckling, but absence of discrete cutaneous or plexiform neurofibromas, Lisch nodules, typical NF1 osseous lesions or symptomatic optic gliomas. Facial features in half of the individuals were suggestive of Noonan syndrome. Our finding and revision of the literature consistently indicate that the c.5425C>T change is associated with a distinctive, mild form of NF1, providing new data with direct impact on genetic counseling and patient management.
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U2 - 10.1038/ejhg.2014.243
DO - 10.1038/ejhg.2014.243
M3 - Article
AN - SCOPUS:84937517366
VL - 23
SP - 1068
EP - 1071
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 8
ER -