MSX2 copy number increase and craniosynostosis: copy number variation detected by array comparative genomic hybridization

Pelegrino, Karla de Oliveira; Sugayama, Sofia Mizuho Miura; Lezirovitz, Karina; Catelani, Ana Lúcia; Kok, Fernando; Chauffaille, Maria de Lourdes Lopes Ferrari

doi:10.6061/clinics/2012(08)23

Cited by 7 publications

(3 citation statements)

References 18 publications

(20 reference statements)

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“…BMP signaling has been recognized as an important patterning signal for neural crest formation (Liem, Tremml, Roelink, & Jessell, 1995;Trainor, Melton, & Manzanares, 2003;Tribulo, Aybar, Nguyen, Mullins, & Mayor, 2003). Gain of function mutations in Msx2, a transcription factor regulated by BMP-SMAD signaling, leads to craniosynostosis (Liu et al, 1995;Pelegrino et al, 2012). Noggin, an antagonist of BMP, is expressed in patent sutures and ectopic expression prevents normal fusion of posterior frontal suture (Greenwald et al, 2001;Warren et al, 2003).…”

mentioning

confidence: 99%

Rapamycin rescues BMP mediated midline craniosynostosis phenotype through reduction of mTOR signaling in a mouse model

Kramer

Yang

Swanson³

et al. 2018

Genesis

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Craniosynostosis is defined as congenital premature fusion of one or more cranial sutures. While the genetic basis for about 30% of cases is known, the causative genes for the diverse presentations of the remainder of cases are unknown. The recently discovered cranial suture stem cell population affords an opportunity to identify early signaling pathways that contribute to craniosynostosis. We previously demonstrated that enhanced BMP signaling in neural crest cells (caA3 mutants) leads to premature cranial suture fusion resulting in midline craniosynostosis. Since enhanced mTOR signaling in neural crest cells leads to craniofacial bone lesions, we investigated the extent to which mTOR signaling is involved in the pathogenesis of BMP-mediated craniosynostosis by affecting the suture stem cell population. Our results demonstrate a loss of suture stem cells in the caA3 mutant mice by the newborn stage. We have found increased activation of mTOR signaling in caA3 mutant mice during embryonic stages, but not at the newborn stage. Our study demonstrated that inhibition of mTOR signaling via rapamycin in a time specific manner partially rescued the loss of the suture stem cell population. This study provides insight into how enhanced BMP signaling regulates suture stem cells via mTOR activation.

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mentioning

confidence: 99%

Rapamycin rescues BMP mediated midline craniosynostosis phenotype through reduction of mTOR signaling in a mouse model

Kramer

Yang

Swanson³

et al. 2018

Genesis

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“…Diversos estudios han demostrado que la elevación de dosis de MSX2 es suficiente para causar craneosinostosis, pero no otro tipo de malformaciones más severas. [10][11][12] Además de MSX2, se sabe que el gen FGFR4 (fibroblast growth factor receptor 4) también se asocia a craneosinostosis, pero a diferencia de MSX2, FGFR4 también se relaciona con otras alteraciones óseas como agenesia radial y ausencia de pulgares. 2,13 Los genes de la familia FGFR están involucrados en procesos celulares críticos incluyendo regulación del ciclo celular, migración, metabolismo, supervivencia, proliferación y diferenciación celular.…”

Section: Discussionunclassified

Duplicación 5q34q35.3 que involucra el gen NSD1: región delimitada por microarreglos de hibridación genómica comparativa. A propósito de un caso

et al. 2016

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La duplicación de la región 5q34q35.3 se ha asociado a un fenotipo inverso de síndrome de Sotos, por contener el gen NSD1 en doble dosis. Se presenta a una paciente con retraso global del desarrollo, peso y talla bajos y dismorfias. Cuenta con antecedente de corrección quirúrgica por defectos de septación auriculoventricular (CIA y CIV), así como remodelación por antecedente de cráneo en trébol. El cariotipo con bandas G mostró un resultado 46,XX,add(5)(q35), y para confirmar el origen del material adicional se utilizó sonda de FISH WCP para el cromosoma 5 [46,XX,add(5)(q35).ish dup(5)(q35)(wcp5+)]. Para definir puntos de ruptura y realizar correlación genotipo fenotipo se realizó microarreglo CytoScan HD de Affymetrix, que confirmó la duplicación intersticial de novo de 14Mb 46,XX,add(5)(q35). arr[hg19] 5q34q35.3(163,110,984-177,227,216x3,177,259,401- 179,330,764x3,179,346,465 180,719,789x3)dn, que contiene 80 genes (USCS genome browser, NCBI36/hg19). La descripción de este caso es importante para complementar la delineación del fenotipo, mediante la correlación con la región de la duplicación a nivel de nucleótidos. Cabe resaltar que la paciente demuestra la importancia y la utilidad de las nuevas técnicas de citogenética molecular, con las cuales es posible el análisis detallado de los genes localizados en la región 5q involucrada, así como su correlación con las manifestaciones clínicas.

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“…MSX2 together with MSX1 is detectable in the developing craniofacial skeleton, including the maxilla, mandible, teeth germs and Meckel’s cartilage [ 7 ]. Msx2-null mutant mice show a phenotype characterized by defective amelogenesis, tooth root dysmorphology and other abnormalities in teeth [ 8 ], skull ossification defects, persistent calvarial foramen and defects in endochondral ossification [ 9 ]. In humans MSX2 gene mutations are associated with Boston type craniosynostosis [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Cleft Candidate Genes and Their Products in Human Unilateral Cleft Lip Tissue

2021

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Cleft lip and palate are common congenital pathologies that affect the human population worldwide. The formation of cleft lip is associated with multiple genes and their coded proteins, which regulate the development of craniofacial region, but the exact role of these factors is not always clear. The use of morphological studies for evaluation of human cleft-affected tissue has been limited because of insufficiency of available pathological material. The aim of this study was to detect and compare the immunohistochemical expression of cleft candidate gene coded proteins (DLX4, MSX2, HOXB3, SHH, PAX7, SOX3, WNT3A, and FOXE1) in the non-syndromic unilateral cleft lip patient tissue and control group tissue. A semiquantitative counting method was used to evaluate the tissue in biotin-streptavidin-stained slides. Statistically significant differences between the patient and control groups were found for the number of immunoreactive structures for SHH (p = 0.019) and FOXE1 (p = 0.011) in the connective tissue and SOX3 (p = 0.012) in the epithelium. Multiple statistically significant very strong and strong correlations were found between the immunoreactives in cleft-affected tissue. These significant differences and various correlations indicate that multiple morphopathogenetic pathways are possibly involved in unilateral cleft lip pathogenesis. Therefore, we further discuss these possible interactions.

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MSX2 copy number increase and craniosynostosis: copy number variation detected by array comparative genomic hybridization

Cited by 7 publications

References 18 publications

Rapamycin rescues BMP mediated midline craniosynostosis phenotype through reduction of mTOR signaling in a mouse model

Rapamycin rescues BMP mediated midline craniosynostosis phenotype through reduction of mTOR signaling in a mouse model

Duplicación 5q34q35.3 que involucra el gen NSD1: región delimitada por microarreglos de hibridación genómica comparativa. A propósito de un caso

Cleft Candidate Genes and Their Products in Human Unilateral Cleft Lip Tissue

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