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: Fiorella Gurrieri, Maria Luigia Cavaliere, Anita Wischmeijer, Corrado Mammì, Giovanni Neri, Maria Antonietta Pisanti, Giulia Rodella, Carmelo Laganà, Manuela Priolo
• Journal: European journal of medical genetics (Eur J Med Genet) Vol. 58 Issue 9 Pg. 488-91 (Sep 2015) ISSN: 1878-0849 [Electronic] Netherlands
• PMID: 26193383 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Chemical References

• DNA-Binding Proteins
• Intracellular Signaling Peptides and Proteins
• NFI Transcription Factors
• NFIX protein, human
• Nuclear Proteins
• Histone Methyltransferases
• Histone-Lysine N-Methyltransferase
• NSD1 protein, human

Topics

• Abnormalities, Multiple (diagnosis, genetics)
• Bone Diseases, Developmental (diagnosis, genetics)
• Child
• Craniofacial Abnormalities (diagnosis, genetics)
• DNA-Binding Proteins (genetics, metabolism)
• Developmental Disabilities (diagnosis, genetics)
• Female
• Genetic Testing
• Histone Methyltransferases
• Histone-Lysine N-Methyltransferase
• Humans
• Infant
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• Male
• Mutation, Missense
• NFI Transcription Factors (genetics, metabolism)
• Nuclear Proteins (genetics, metabolism)
• Phenotype
• Septo-Optic Dysplasia (diagnosis, genetics)
• Sotos Syndrome (diagnosis, genetics)