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

Martı́nez, Francisco; Marín-Reina, Purificación; Calvo, A. Sanchis; Pérez-Aytés, Antonio; Oltra, Silvestre; Roselló, Mónica; Mayo, Sonia; Monfort, Sandra; Pantoja, Jorge; Orellana, Carmen

doi:10.1038/pr.2015.135

Cited by 38 publications

(41 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…De etiología desconocida, se han descrito mutaciones "de novo" en los exones 2 y 6-10 del gen NFIX 2 . Fue descrita por primera vez en 1971 3 y cursa con una maduración ósea acelerada, rasgos dismórficos (frente prominente, macizo facial pequeño, ojos prominentes, escleróticas azules, narinas antevertidas, puente nasal plano, micrognatia, labios evertidos), alteraciones cerebrales (hipoplasia del cuerpo calloso) 2,5,7,8 , baja talla, cifoescoliosis 8 , defectos cutáneos en la pigmentación 9 , pubertad precoz central y rodete subaórtico 10 , y en ocasiones alteraciones en el desarrollo neuropsicomotor 3,4,7 . El compromiso respiratorio por obstrucción de las vías altas es la patología principal que produce infecciones respiratorias de repetición, condiciona un déficit de crecimiento y disminuye las posibilidades de supervivencia hasta la etapa adulta 5,7 incluyendo un alto riesgo de sufrir complicaciones anestésicas en relación con el mantenimiento de las vías aéreas 6 .…”

Section: Introductionunclassified

Sindrome de Marshall- Smith en mujer adulta. Nuevos retos en anticoncepción

Borque

et al. 2017

Rev. chil. obstet. ginecol.

View full text Add to dashboard Cite

RESUMENSe presenta el caso de una mujer de 38 años con Síndrome de Marshall-Smith. Se trata de una enfermedad rara de etiología desconocida, cuyas características incluyen anomalías craneofaciales, maduración ósea acelerada, alteraciones en el desarrollo neurológico y en las vías respiratorias con compromiso de la vía aérea y escasa supervivencia a largo plazo debido a problemas respiratorios. Sin embargo, los avances en el soporte respiratorio han permitido que algunos pacientes lleguen a la etapa adulta. Nuestra paciente, sin retraso intelectual ni psicomotor, solicita método anticonceptivo. Los pacientes con enfermedades raras necesitan ser atendidos con especial dedicación intentando reducir al mínimo la transmisión genética de dichas entidades, y mejorando al máximo su calidad de vida. Se ofrece un método anticonceptivo reversible de larga duración, sin riesgos para la evolución de su patología respiratoria, y atendiendo a los criterios medicos de elegibilidad de método anticonceptivo de la OMS, se indica la utilización de un implante subdérmico de etonogestrel. Con un perfil de seguridad y farmacocinética equivalente a los métodos de solo gestágeno y mayor comodidad. PALABRAS CLAVE:Síndrome de Marshall-Smith, Anticoncepción Reversible de larga duración. ABSTRACTA 38-year-old female patient with a history of Marshall-Smith syndrome is reported. It is a rare congenital disorder of unknown aetiology, which features include craneo facial dysmorphism, accelerated bone maturation, neurodevelopmental abnormalities, and upper and lower airways compromise. Long term survival is a problem due to respiratory complications, but it has decreased since airway support has improved, and that allows survival into adulthood. Our patient has neither intelectual nor psychomotor delay, so she asks for contraception method. As a rare genetic condition it needs to be attended with special consideration in order to reduce the disorder's transmission and to increase the life's quality of patients. A secure contraception method should be offered with no risk at all, attending to medical elegibility criteria for contraception use. We considered progestogen-only options and the patient's choice was etonogestrel subcutaneous implant.

show abstract

Section: Introductionunclassified

Sindrome de Marshall- Smith en mujer adulta. Nuevos retos en anticoncepción

Borque

et al. 2017

Rev. chil. obstet. ginecol.

View full text Add to dashboard Cite

show abstract

“…In ~90% of Sotos syndrome cases, mutations occur in the gene encoding nuclear receptor-binding SET domain containing protein 1 ( NSD1 ), 1, 2,3 located on chromosome 5q35. Recently, the NFIX gene on chromosome 19p13, which encodes nuclear factor I/X, was reported as a causative gene for Sotos-like phenotypes (known as Sotos syndrome 2 or Malan syndrome (OMIM #614753)), 4,5, 6 and a total of such 33 patients aged 1–27 years have been reported. Most cases have been sporadic owing to the severity of the phenotype.…”

mentioning

confidence: 99%

“…4,5, 6 Malan et al 4 speculated that differences in phenotype consequences are due to differences in the fate of the mRNAs; the haploinsufficiency due to nonsense-mediated mRNA decay (NMD) and the dominant-negative effect of putative truncated proteins likely lead to Malan syndrome and Marshall–Smith syndrome, respectively. Consistent with these observations, in the present case, the single-base adenine (A) insertion mutation within exon 2 produced frameshift and a premature termination codon, and thus, the mutant mRNAs are presumably degradated by NMD.…”

mentioning

confidence: 99%

A novel mutation of NFIX causes Sotos-like syndrome (Malan syndrome) complicated with thoracic aortic aneurysm and dissection

et al. 2017

View full text Add to dashboard Cite

Malan syndrome has recently been characterized to present Sotos-like phenotypes, such as intellectual disability and macrocephaly, with mutations in the NFIX gene. Herein, we report a 38-year-old patient with a novel single adenine insertion mutation in exon 2 of the NFIX gene (c.290_291insA). He developed early-onset thoracic aortic aneurysm and dissection, which was a rare complication but deserves particular attention in relatively long-lived patients with Sotos-like phenotypes.

show abstract

“…Marshall-Smith syndrome (Malan et al, 2010;Martinez et al, 2015). As to which of these two disorders arises from an NFIX mutation, genotype-phenotype correlations have shown that this depends upon the location of the mutation within the NFIX gene body and subsequently, whether the mutation leads to a loss-of-or dominant-negative function.…”

Section: Nfix Mutations Cause Sotos Syndrome or Marshall-smith Syndromementioning

confidence: 99%

“…For example, heterozygous NFIX deletions or nonsense/missense mutations in the DNA-binding/dimerisation domain (exon 2/3) of NFIX result in a loss of protein activity and Sotos Syndrome (Malan et al, 2010;Yoneda et al, 2012;Gurrieri et al, 2015;Klaassens et al, 2015) and thus is sometimes referred to as a NFIX haploinsufficiency. In contrast, heterozygous frameshift or splice-site variants in exons 6-10 of NFIX, positioned close to the C-terminus transactivation domain, escape nonsense-mediated decay (Malan et al, 2010;Klaassens et al, 2015;Martinez et al, 2015) and engender a Marshall-Smith Syndrome. It is thought that the mutated allele in Marshall-Smith Syndrome forms a dominantnegative protein that competes with the wild-type version of the NFIX protein (Malan et al, 2010 (Kurotaki et al, 2002).…”

Section: Nfix Mutations Cause Sotos Syndrome or Marshall-smith Syndromementioning

confidence: 99%

The function of NFIX during developmental and adult neurogenesis

Harris¹

View full text Add to dashboard Cite

Understanding the transcription factor proteins that control the biology of neural stem cells during embryogenesis provides insight into brain development as well as neurodevelopmental disorders.Likewise, studying the function of transcription factors in adult neural stem cells allows us to appreciate the dynamics of these cells and their contribution to normal cognitive function. It also provides a knowledge base so as to one day harness the activity of adult neural stem cells to treat degenerative conditions of the nervous system.One family of transcription factors key to brain development are the Nuclear Factor Ones (NFIs).Comprised of four members in mammals (NFIA, NFIB, NFIC and NFIX) these proteins promote both neuronal and glial differentiation during mouse forebrain development, and in general, appear to have a highly similar function. This thesis addressed two outstanding questions regarding the function of one these proteins, NFIX, in mouse neural stem cell biology. The first question concerned refining our understanding of NFIX function during forebrain development by determining, which stage of neuron differentiation, from a stem cell to a mature neuron, is The second question I addressed in this thesis, was that if NFI proteins are so important for regulating neural stem cell biology during brain development, then do they also regulate adult neural stem cell biology? I addressed this question by breeding inducible, conditional mice to allow for deletion of Nfix from adult hippocampal neural stem cells and separately, immature neurons. I found that NFIX is essential for adult-borne neuron differentiation, so that in the absence of NFIX, mature neurons are not generated and behavioural deficits ensue. Mechanistically, we found that NFIX is essential for primary dendrite formation, and that without NFIX a proportion of adult hippocampal progenitors switch fate to become oligodendrocytes or aberrantly express increased levels of oligodendrocyte mRNA. In addition to demonstrating the absolute requirement of the NFIX protein for the generation of adult-borne neurons, these findings reveal the surprising tri-

show abstract

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

Cited by 38 publications

References 10 publications

Sindrome de Marshall- Smith en mujer adulta. Nuevos retos en anticoncepción

Sindrome de Marshall- Smith en mujer adulta. Nuevos retos en anticoncepción

A novel mutation of NFIX causes Sotos-like syndrome (Malan syndrome) complicated with thoracic aortic aneurysm and dissection

The function of NFIX during developmental and adult neurogenesis

Contact Info

Product

Resources

About