NFIX mutations affecting the DNA-binding domain cause a peculiar overgrowth syndrome (Malan syndrome): a new patients series

Fiorella Gurrieri; Maria Luigia Cavaliere; Anita Wischmeijer; Corrado Mammì; Giovanni Neri; Maria Antonietta Pisanti; Giulia Rodella; Carmelo Laganà; Manuela Priolo

doi:10.1016/j.ejmg.2015.06.009

NFIX mutations affecting the DNA-binding domain cause a peculiar overgrowth syndrome (Malan syndrome): a new patients series

Eur J Med Genet. 2015 Sep;58(9):488-91. doi: 10.1016/j.ejmg.2015.06.009. Epub 2015 Jul 17.

Authors

Fiorella Gurrieri¹, Maria Luigia Cavaliere², Anita Wischmeijer³, Corrado Mammì⁴, Giovanni Neri¹, Maria Antonietta Pisanti², Giulia Rodella⁵, Carmelo Laganà⁴, Manuela Priolo⁶

Affiliations

¹ Istituto di Genetica Medica, Università Cattolica S. Cuore, Roma, Italy.
² UO Genetica Medica, Cardarelli Hospital, Naples, Italy.
³ 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.
⁴ UO Genetica Medica, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy.
⁵ UO Genetica Medica, Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi, Università di Bologna, Bologna, Italy.
⁶ UO Genetica Medica, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy. Electronic address: prioloma@libero.it.

PMID: 26193383
DOI: 10.1016/j.ejmg.2015.06.009

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.

Keywords: DNA-Binding/dimerization domain; MH1 domain; NFIX; Overgrowth syndrome.

Publication types

Case Reports

MeSH terms

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

Substances

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

Supplementary concepts

Marshall-Smith syndrome