19p13 microduplications encompassing NFIX are responsible for intellectual disability, short stature and small head circumference

Aurélien Trimouille, Nada Houcinat, Marie Laure Vuillaume, Patricia Fergelot, Patricia Fergelot, Cécile Boucher, Jérôme Toutain, Cédric Le Caignec, Marie Vincent, Mathilde Nizon, Joris Andrieux, Clémence Vanlerberghe, Bruno Delobel, Bénédicte Duban, Sahar Mansour, Emma Baple, Colina McKeown, Gemma Poke, Kate Robertshaw, Eve FifieldAntonella Fabretto, Vanna Pecile, Paolo Gasparini, Paolo Gasparini, Marco Carrozzi, Didier Lacombe, Didier Lacombe, Benoît Arveiler, Benoît Arveiler, Caroline Rooryck, Caroline Rooryck, Sébastien Moutton

Research output: Contribution to journalArticlepeer-review


© 2017 European Society of Human Genetics. Syndromes caused by copy number variations are described as reciprocal when they result from deletions or duplications of the same chromosomal region. When comparing the phenotypes of these syndromes, various clinical features could be described as reversed, probably due to the opposite effect of these imbalances on the expression of genes located at this locus. The NFIX gene codes for a transcription factor implicated in neurogenesis and chondrocyte differentiation. Microdeletions and loss of function variants of NFIX are responsible for Sotos syndrome-2 (also described as Malan syndrome), a syndromic form of intellectual disability associated with overgrowth and macrocephaly. Here, we report a cohort of nine patients harboring microduplications encompassing NFIX. These patients exhibit variable intellectual disability, short stature and small head circumference, which can be described as a reversed Sotos syndrome-2 phenotype. Strikingly, such a reversed phenotype has already been described in patients harboring microduplications encompassing NSD1, the gene whose deletions and loss-of-function variants are responsible for classical Sotos syndrome. Even though the type/contre-type concept has been criticized, this model seems to give a plausible explanation for the pathogenicity of 19p13 microduplications, and the common phenotype observed in our cohort.
Original languageEnglish
Pages (from-to)85-93
Number of pages9
JournalEuropean Journal of Human Genetics
Issue number1
Publication statusPublished - Jan 1 2018


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