M. Cecconi and F. Forzano contributed equally to this work.
Mutation analysis of the NSD1 gene in a group of 59 patients with congenital overgrowth†
Article first published online: 1 MAR 2005
Copyright © 2005 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 134A, Issue 3, pages 247–253, 30 April 2005
How to Cite
Cecconi, M., Forzano, F., Milani, D., Cavani, S., Baldo, C., Selicorni, A., Pantaleoni, C., Silengo, M., Ferrero, G.B., Scarano, G., Della Monica, M., Fischetto, R., Grammatico, P., Majore, S., Zampino, G., Memo, L., Cordisco, E. L., Neri, G., Pierluigi, M., Bricarelli, F. D., Grasso, M. and Faravelli, F. (2005), Mutation analysis of the NSD1 gene in a group of 59 patients with congenital overgrowth. Am. J. Med. Genet., 134A: 247–253. doi: 10.1002/ajmg.a.30492
- Issue published online: 18 MAR 2005
- Article first published online: 1 MAR 2005
- Manuscript Accepted: 18 OCT 2004
- Manuscript Received: 15 JUN 2004
- Telethon Italia. Grant Number: C51
- Murst (to G.B.F. and M.S.)
- Compagnia di San Paolo, Torino (to G.B.F.)
- Sotos syndrome;
Sotos syndrome is characterized by pre- and post-natal overgrowth, typical craniofacial features, advanced bone age, and developmental delay. Some degree of phenotypic overlap exists with other overgrowth syndromes, in particular with Weaver syndrome. Sotos syndrome is caused by haploinsufficiency of the NSD1 (nuclear receptor SET domain containing gene 1) gene. Microdeletions involving the gene are the major cause of the syndrome in Japanese patients, whereas intragenic mutations are more frequent in nonJapanese patients. NSD1 aberrations have also been described in some patients diagnosed as Weaver syndrome. Some authors have suggested a certain degree of genotype–phenotype correlation, with a milder degree of overgrowth, a more severe mental retardation, and a higher frequency of congenital anomalies in microdeleted patients. Data on larger series are needed to confirm this suggestion. We report here on microdeletion and mutation analysis of NSD1 in 59 patients with congenital overgrowth. Fourteen novel mutations, two previously described and one microdeletion were identified. All patients with a NSD1 mutation had been clinically classified as “classical Sotos,” although their phenotype analysis demonstrated that some major criteria, such as overgrowth and macrocephaly, could be absent. All patients with confirmed mutations shared the typical Sotos facial gestalt. A high frequency of congenital heart defects was present in patients with intragenic mutations, supporting the relevance of the NSD1 gene in the pathogenesis of this particular defect. © 2005 Wiley-Liss, Inc.