Legius syndrome in fourteen families

Ellen Denayer (1) , Magdalena Chmara (1) , Hilde Brems (1) , Anneke Maat-Kievit (2) , Yolande van Bever (3) , Ans M.W. van den Ouweland (4) , Rick van Minckelen (4) , Arja de Goede (5) , Rianne Oostenbrink (5) , Phillis Lakeman (6) , Eline Beert (1) , Takuma Ishizaki (7) , Tomoaki Mori (7) , Kathelijn Keymolen (8) , Jenneke van den Ende (9) , Elisabeth Mangold (10) , Sirkku Peltonen (11) , Glen Brice (12) , Julia Rankin (13) , Karin Y. van Spaendonck (14) , Akihiko Yoshimura (7) , Eric Legius (15)

1 Human Genetics
2 Department of Clinical Genetics
3 Department of Clinical Genetics
4 Clinical Genetics
5 Pediatrics
6 2Department of Clinical Genetics
7 Microbiology and Immunology
8 Center Medical Genetics
9 Biomedical Sciences
10 Institute of Human Genetics
11 Dermatology
12 South West Thames Regional Genetics Unit
13 Clinical Genetics
14 Genetics
15 Human Genetics

Legius syndrome presents as an autosomal dominant condition characterized by café-au-lait macules with or without freckling and sometimes a Noonan-like appearance and/or learning difficulties. It is caused by germline loss-of-function SPRED1 mutations and is a member of the RAS-MAPK pathway syndromes. Most mutations result in a truncated protein and only a few inactivating missense mutations have been reported. Since only a limited number of patients has been reported up until now, the full clinical and mutational spectrum is still unknown. We report mutation data and clinical details in fourteen new families with Legius syndrome. Six novel germline mutations are described. The Trp31Cys mutation is a new pathogenic SPRED1 missense mutation. Clinical details in the 14 families confirmed the absence of neurofibromas, and Lisch nodules, and the absence of a high prevalence of central nervous system tumors. We report white matter T2 hyperintensities on brain MRI scans in 2 patients and a potential association between postaxial polydactyly and Legius syndrome.

Mots clés: Life Sciences

Ellen Denayer, Magdalena Chmara, Hilde Brems, Anneke Maat-Kievit, Yolande van Bever, et al.. Legius syndrome in fourteen families. Human Mutation, 2010, 32 (1), ⟨10.1002/humu.21404⟩. ⟨hal-00613756⟩