A series of 38 novel germline and somatic mutations ofNIPBLin Cornelia de Lange syndrome

Autor: Hervé Testard, Martine Doco-Fenzy, Alice Goldenberg, Fabienne Prieur, Caroline Michot, Marcia Henry, Sandrine Marlin, Sophie Blesson, Clarisse Baumann, Valérie Cormier-Daire, Philippe Loget, Sylvie Odent, Marlène Rio, Anne-Lise Delezoide, Andrée Delahaye-Duriez, Jean-Paul Bonnefont, Anne Dieux-Coeslier, Audrey Putoux, Marie-Pierre Cordier-Alex, Ghislaine Plessis, Valérie Layet, Albert David, Mathilde Nizon, Bettina Bessières, Jelena Martinovic, Laurent Pasquier, Anne Bazin, Laurence Faivre
Rok vydání: 2016
Předmět:
Zdroj: Clinical Genetics. 89:584-589
ISSN: 0009-9163
DOI: 10.1111/cge.12720
Popis: Cornelia de Lange syndrome is a multisystemic developmental disorder mainly related to de novo heterozygous NIPBL mutation. Recently, NIPBL somatic mosaicism has been highlighted through buccal cell DNA study in some patients with a negative molecular analysis on leukocyte DNA. Here, we present a series of 38 patients with a Cornelia de Lange syndrome related to an heterozygous NIPBL mutation identified by Sanger sequencing. The diagnosis was based on the following criteria: 1) intrauterine growth retardation and postnatal short stature, 2) feeding difficulties and/or gastro-oesophageal reflux, 3) microcephaly, 4) intellectual disability and 5) characteristic facial features. We identified 37 novel NIPBL mutations including 34 in leukocytes and three in buccal cells only. All mutations shown to have arisen de novo when parent blood samples were available. The present series confirms the difficulty in predicting the phenotype according to the NIPBL mutation. Until now, somatic mosaicism has been observed for twenty cases which does not seem to be consistently associated with a milder phenotype. Besides, several reports support a postzygotic event for those cases. Considering these elements, we recommend a first-line buccal cell DNA analysis in order to improve gene testing sensitivity in Cornelia de Lange syndrome and genetic counseling
Databáze: OpenAIRE
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