TY - JOUR
T1 - Genotype-phenotype correlation in patients suspected of having Sotos syndrome
AU - de Boer, Lonneke
AU - Kant, Sarina G.
AU - Karperien, Marcel
AU - van Beers, Lotte
AU - Tjon, Jennifer
AU - Vink, Geraldine R.
AU - van Tol, Dewy
AU - Dauwerse, Hans
AU - le Cessie, Saskia
AU - Beemer, Frits A.
AU - van der Burgt, Ineke
AU - Hamel, Ben C. J.
AU - Hennekam, Raoul C.
AU - Kuhnle, Ursula
AU - Mathijssen, Inge B.
AU - Veenstra-Knol, Hermine E.
AU - Stumpel, Connie T. Schrander
AU - Breuning, Martijn H.
AU - Wit, Jan M.
PY - 2004
Y1 - 2004
N2 - Background: Deletions and mutations in the NSD1 gene are the major cause of Sotos syndrome. We wanted to evaluate the genotype-phenotype correlation in patients suspected of having Sotos syndrome and determine the best discriminating parameters for the presence of a NSD1 gene alteration. Methods: Mutation and fluorescence in situ hybridization analysis was performed on blood samples of 59 patients who were clinically scored into 3 groups. Clinical data were compared between patients with and without NSD1 alterations. With logistic regression analysis the best combination of predictive variables was obtained. Results: In the groups of typical, dubious and atypical Sotos syndrome, 81, 36 and 0% of the patients, respectively, showed NSD1 gene alterations. Four deletions were detected. In 23 patients (2 families) 19 mutations were detected (1 splicing defect, 3 non-sense, 7 frameshift and 8 missense mutations). The best predictive parameters for a NSD1 gene alteration were frontal bossing, down-slanted palpebral fissures, pointed chin and overgrowth. Higher incidences of feeding problems and cardiac anomalies were found. The parameters, delayed development and advanced bone age, did not differ between the 2 subgroups. Conclusions: In our patients suspected of having Sotos syndrome, facial features and overgrowth were highly predictive of a NSD1 gene aberration, whereas developmental delay and advanced bone age were not. Copyright (C) 2004 S. Karger AG, Basel
AB - Background: Deletions and mutations in the NSD1 gene are the major cause of Sotos syndrome. We wanted to evaluate the genotype-phenotype correlation in patients suspected of having Sotos syndrome and determine the best discriminating parameters for the presence of a NSD1 gene alteration. Methods: Mutation and fluorescence in situ hybridization analysis was performed on blood samples of 59 patients who were clinically scored into 3 groups. Clinical data were compared between patients with and without NSD1 alterations. With logistic regression analysis the best combination of predictive variables was obtained. Results: In the groups of typical, dubious and atypical Sotos syndrome, 81, 36 and 0% of the patients, respectively, showed NSD1 gene alterations. Four deletions were detected. In 23 patients (2 families) 19 mutations were detected (1 splicing defect, 3 non-sense, 7 frameshift and 8 missense mutations). The best predictive parameters for a NSD1 gene alteration were frontal bossing, down-slanted palpebral fissures, pointed chin and overgrowth. Higher incidences of feeding problems and cardiac anomalies were found. The parameters, delayed development and advanced bone age, did not differ between the 2 subgroups. Conclusions: In our patients suspected of having Sotos syndrome, facial features and overgrowth were highly predictive of a NSD1 gene aberration, whereas developmental delay and advanced bone age were not. Copyright (C) 2004 S. Karger AG, Basel
U2 - https://doi.org/10.1159/000081063
DO - https://doi.org/10.1159/000081063
M3 - Article
C2 - 15452385
SN - 0301-0163
VL - 62
SP - 197
EP - 207
JO - Hormone research
JF - Hormone research
IS - 4
ER -