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 Fifield & 12 others Antonella Fabretto, Vanna Pecile, Paolo Gasparini, Paolo Gasparini, Marco Carrozzi, Didier Lacombe, Didier Lacombe, Benoît Arveiler, Benoît Arveiler, Caroline Rooryck, Caroline Rooryck, Sébastien Moutton

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Abstract

© 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.
LanguageEnglish
Pages85-93
Number of pages9
JournalEuropean Journal of Human Genetics
Volume26
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

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Sotos Syndrome
Intellectual Disability
Head
Phenotype
Chromosome Duplication
Megalencephaly
Neurogenesis
Gene Deletion
Medical Genetics
Chondrocytes
Virulence
Transcription Factors
Gene Expression
Genes

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19p13 microduplications encompassing NFIX are responsible for intellectual disability, short stature and small head circumference. / Trimouille, Aurélien; Houcinat, Nada; Vuillaume, Marie Laure; Fergelot, Patricia; Fergelot, Patricia; Boucher, Cécile; Toutain, Jérôme; Caignec, Cédric Le; Vincent, Marie; Nizon, Mathilde; Andrieux, Joris; Vanlerberghe, Clémence; Delobel, Bruno; Duban, Bénédicte; Mansour, Sahar; Baple, Emma; McKeown, Colina; Poke, Gemma; Robertshaw, Kate; Fifield, Eve; Fabretto, Antonella; Pecile, Vanna; Gasparini, Paolo; Gasparini, Paolo; Carrozzi, Marco; Lacombe, Didier; Lacombe, Didier; Arveiler, Benoît; Arveiler, Benoît; Rooryck, Caroline; Rooryck, Caroline; Moutton, Sébastien.

In: European Journal of Human Genetics, Vol. 26, No. 1, 01.01.2018, p. 85-93.

Research output: Contribution to journalArticle

Trimouille, A, Houcinat, N, Vuillaume, ML, Fergelot, P, Fergelot, P, Boucher, C, Toutain, J, Caignec, CL, Vincent, M, Nizon, M, Andrieux, J, Vanlerberghe, C, Delobel, B, Duban, B, Mansour, S, Baple, E, McKeown, C, Poke, G, Robertshaw, K, Fifield, E, Fabretto, A, Pecile, V, Gasparini, P, Gasparini, P, Carrozzi, M, Lacombe, D, Lacombe, D, Arveiler, B, Arveiler, B, Rooryck, C, Rooryck, C & Moutton, S 2018, '19p13 microduplications encompassing NFIX are responsible for intellectual disability, short stature and small head circumference' European Journal of Human Genetics, vol. 26, no. 1, pp. 85-93. https://doi.org/10.1038/s41431-017-0037-7
Trimouille, Aurélien ; Houcinat, Nada ; Vuillaume, Marie Laure ; Fergelot, Patricia ; Fergelot, Patricia ; Boucher, Cécile ; Toutain, Jérôme ; Caignec, Cédric Le ; Vincent, Marie ; Nizon, Mathilde ; Andrieux, Joris ; Vanlerberghe, Clémence ; Delobel, Bruno ; Duban, Bénédicte ; Mansour, Sahar ; Baple, Emma ; McKeown, Colina ; Poke, Gemma ; Robertshaw, Kate ; Fifield, Eve ; Fabretto, Antonella ; Pecile, Vanna ; Gasparini, Paolo ; Gasparini, Paolo ; Carrozzi, Marco ; Lacombe, Didier ; Lacombe, Didier ; Arveiler, Benoît ; Arveiler, Benoît ; Rooryck, Caroline ; Rooryck, Caroline ; Moutton, Sébastien. / 19p13 microduplications encompassing NFIX are responsible for intellectual disability, short stature and small head circumference. In: European Journal of Human Genetics. 2018 ; Vol. 26, No. 1. pp. 85-93.
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AU - Houcinat, Nada

AU - Vuillaume, Marie Laure

AU - Fergelot, Patricia

AU - Fergelot, Patricia

AU - Boucher, Cécile

AU - Toutain, Jérôme

AU - Caignec, Cédric Le

AU - Vincent, Marie

AU - Nizon, Mathilde

AU - Andrieux, Joris

AU - Vanlerberghe, Clémence

AU - Delobel, Bruno

AU - Duban, Bénédicte

AU - Mansour, Sahar

AU - Baple, Emma

AU - McKeown, Colina

AU - Poke, Gemma

AU - Robertshaw, Kate

AU - Fifield, Eve

AU - Fabretto, Antonella

AU - Pecile, Vanna

AU - Gasparini, Paolo

AU - Gasparini, Paolo

AU - Carrozzi, Marco

AU - Lacombe, Didier

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AU - Arveiler, Benoît

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AU - Rooryck, Caroline

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