title: NFIX mutations affecting the DNA-binding domain cause a peculiar overgrowth syndrome (Malan syndrome): a new patients series.
abstract: The Nuclear Factor I-X (NFIX) is a member of the nuclear factor I (NFI) protein family and is deleted or mutated in a subset of patients with a peculiar overgrowth condition resembling Sotos Syndrome as well as in patients with Marshall-Smith syndrome. We identified three additional patients with this phenotype each carrying a different new mutation affecting the DNA-binding/dimerization domain of the NFIX protein. The present report further adds weight to the hypothesis that mutations in DNA-binding/dimerization domain are likely to cause haploinsufficiency of the NFIX protein and confirms that NFIX is the second gene that should be tested in individuals with overgrowth conditions resembling Sotos syndrome, previously tested negative for NSD1 mutations. We then propose to consider this overgrowth syndrome (namely Malan syndrome) and Marshall-Smith syndrome NFIX-related diseases.
authors.affiliation: Istituto di Genetica Medica, Università Cattolica S. Cuore, Roma, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Gurrieri
authors.affiliation: UO Genetica Medica, Cardarelli Hospital, Naples, Italy.
authors.forename: Maria Luigia
authors.initials: ML
authors.lastname: Cavaliere
authors.affiliation: UO Genetica Medica, Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi, Università di Bologna, Bologna, Italy; SSD Genetica Clinica, Azienda ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.
authors.forename: Anita
authors.initials: A
authors.lastname: Wischmeijer
authors.affiliation: UO Genetica Medica, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Mammì
authors.affiliation: Istituto di Genetica Medica, Università Cattolica S. Cuore, Roma, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Neri
authors.affiliation: UO Genetica Medica, Cardarelli Hospital, Naples, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Pisanti
authors.affiliation: UO Genetica Medica, Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi, Università di Bologna, Bologna, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Rodella
authors.affiliation: UO Genetica Medica, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Laganà
authors.affiliation: UO Genetica Medica, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy. Electronic address: prioloma@libero.it.
authors.forename: Manuela
authors.initials: M
authors.lastname: Priolo
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D001848:Bone Diseases, Developmental / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D020125:Mutation, Missense; D051839:NFI Transcription Factors / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D025962:Septo-Optic Dysplasia / Q000175:diagnosis / Q000235:genetics*; D058495:Sotos Syndrome / Q000175:diagnosis / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051839:NFI Transcription Factors; C000594474:NFIX protein, human; D009687:Nuclear Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human
keywords: DNA-Binding/dimerization domain; MH1 domain; NFIX; Overgrowth syndrome