Legius syndrome in fourteen families

Ellen Denayer, Magdalena Chmara, Hilde Brems, Anneke Maat Kievit, Yolande van Bever, Ans M. W. van den Ouweland, Rick van Minkelen, Arja de Goede-Bolder, Rianne Oostenbrink, Phillis Lakeman, Eline Beert, Takuma Ishizaki, Tomoaki Mori, Kathelijn Keymolen, Jenneke van den Ende, Elisabeth Mangold, Sirkku Peltonen, Glen Brice, Julia Rankin, Karin Y. van Spaendonck-ZwartsAkihiko Yoshimura, Eric Legius, J. van der Ende

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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
Original languageEnglish
Pages (from-to)E1985-E1998
JournalHuman mutation
Issue number1
Publication statusPublished - 2011

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