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Pediatr Res. 2015 Nov;78(5):533-9. doi: 10.1038/pr.2015.135. Epub 2015 Jul 22.

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

Author information

1
Unidad de Genética, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
2
Unidad de Dismorfología, Servicio de Pediatría, Consorcio Hospital General Universitario, Valencia, Spain.
3
Servicio de Pediatría, Hospital Universitario Doctor Peset, Valencia, Spain.
4
CIBER de Enfermedades Raras (CIBERER), U724, Madrid, Spain.
5
Servicio de Neonatología, Unidad de Dismorfologia y Genetica Reproductiva, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
6
Servicio de Pediatría, Hospital La Plana, Villarreal, Castellón, Spain.

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.

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.

PMID:
26200704
DOI:
10.1038/pr.2015.135
[Indexed for MEDLINE]

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