title: Novel mutations of NFIX gene causing Marshall-Smith syndrome or Sotos-like syndrome: one gene, two phenotypes.
abstract: BACKGROUND
  Only 15 point mutations in NFIX gene have been reported so far, nine of them cause the Marshall-Smith syndrome (MSS) and the remaining mutations lead to an overgrowth disorder with a less severe phenotype, defined as Sotos-like.
  
  
  METHODS
  The clinical findings in three patients with MSS and two patients with a Sotos-like phenotype are presented. Analysis of the NFIX gene was performed both by conventional or next-generation sequencing.
  
  
  RESULTS
  Five de novo mutations in NFIX gene were identified, four of them not previously reported. Two frameshift mutations and a donor-splice one caused MSS, while two missense mutations in the DNA binding/dimerisation domain entailed an overgrowth syndrome with some clinical features resembling Sotos syndrome, accompanied by a marfanoid habitus, very low BMI, long narrow face, or arachnodactyly.
  
  
  CONCLUSIONS
  Marshall-Smith mutations are scattered through exons 6-10 of NFIX gene, while most point mutations causing an overgrowth syndrome are clustered in exon 2. Clinical features of this overgrowth syndrome may well be considered an intermediate phenotype between Sotos and Marfan syndromes.
authors.affiliation: Unidad de Genética, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Francisco
authors.identifier: http://orcid.org/0000-0002-0589-2584
authors.initials: F
authors.lastname: Martinez
authors.affiliation: Unidad de Dismorfología, Servicio de Pediatría, Consorcio Hospital General Universitario, Valencia, Spain.
authors.forename: Purificación
authors.initials: P
authors.lastname: Marín-Reina
authors.affiliation: Servicio de Pediatría, Hospital Universitario Doctor Peset, Valencia, Spain.|CIBER de Enfermedades Raras (CIBERER), U724, Madrid, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Sanchis-Calvo
authors.affiliation: Servicio de Neonatología, Unidad de Dismorfologia y Genetica Reproductiva, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Perez-Aytés
authors.affiliation: Unidad de Genética, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Silvestre
authors.initials: S
authors.lastname: Oltra
authors.affiliation: Unidad de Genética, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Roselló
authors.affiliation: Unidad de Genética, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Mayo
authors.affiliation: Unidad de Genética, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Monfort
authors.affiliation: Servicio de Pediatría, Hospital La Plana, Villarreal, Castellón, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Pantoja
authors.affiliation: Unidad de Genética, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Orellana
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001848:Bone Diseases, Developmental / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons; D017809:Fatal Outcome; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D051839:NFI Transcription Factors / Q000235:genetics*; D010641:Phenotype; D025962:Septo-Optic Dysplasia / Q000175:diagnosis / Q000235:genetics*; D058495:Sotos Syndrome / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D051839:NFI Transcription Factors; C000594474:NFIX protein, human