Novel mutations of NFIX gene causing Marshall-Smith syndrome or Sotos-like syndrome: one gene, two phenotypes

Autores de IIS La Fe

• 

  Francisco Martínez Castellano

  Autor

• Purificación Marín Reina

  Autor

• Antonio Pérez Aytes

  Autor

• Juan Silvestre Oltra Soler

  Autor

• Mónica Pilar Roselló Piera

  Autor

• Sonia Mayo De Andres

  Autor

• Sandra Monfort Membrado

  Autor

• Carmen Orellana Alonso

  Autor

Participantes ajenos a IIS La Fe

• Sanchis-Calvo A
• Pantoja J

Grupos

• Investigación Traslacional en Genética

  

  Leader

  Francisco Martínez Castellano

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 frame shift 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. CONCLUSION: 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.

Keywords

• DNA-BINDING/DIMERIZATION DOMAIN; MISSENSE MUTATIONS; OVERGROWTH