Pure de novo partial trisomy 6p in a girl with craniosynostosis

Varvagiannis, Konstantinos; Stefanidou, Amalia; Gyftodimou, Yolanda; Lord, Helen; Williams, Louise; Sarri, Catherine; Pandelia, Effie; Bazopoulou-Kyrkanidou, Euterpe; Noakes, Charlotte; Lester, Tracy; Petersen, Michael B.

doi:10.1002/ajmg.a.35727

Cited by 20 publications

(17 citation statements)

References 33 publications

(35 reference statements)

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“…RUNX2 [Varvagiannis et al, 2013] and BMP5 [Villa et al, 2007] have correctly been proposed to explain craniosynostosis and craniofacial abnormalities; on the other hand, there are cases that have dysmorphic features without the involvement of the RUNX2 and BMP5 genes in the triplicated chromosomal segments. Su et al [2012] suggested 9 other genes: FOXQ1, FOXF2, FOXC1, NRN1, EDN1, ATXN1, DEK , E2F3 , and NRSN1.…”

Section: Discussionmentioning

confidence: 99%

“…Particular findings are generally reported. Villa et al, 2007;Su et al, 2012;Varvagiannis et al, 2013] . Additionally, the translocation can involve different chromosomes, and disruption or deletion of different located genes could have a significant pathogenic effect that contributes to define specific phenotypes ( table 2 ).…”

Section: F 6p21pter/20p13mentioning

confidence: 99%

“…Eligible candidates are the genes IRF4 , BMP5 , BMP6 , RUNX2, FOXQ1,FOXF2,FOXC1,NRN1,EDN1,ATXN1,TFAP2B,VEGFA,DEK oncogene ,E2F3,NRNS1,SERPINB1,SERPINB6,SERPINB9 , and the HLA (major histocompatibility complex) family (A, B, C, E, F, G) [Pearson et al, 1979;Fogu et al, 2007;Mandal et al, 2007; BMP5 was suggested as a candidate gene. The same duplicated region contains the RUNX2 transcription factor [Varvagiannis et al, 2013]. Nevertheless, Maurer et al [2001] reported 1 case with a developmental delay and craniofacial dysmorphisms, but no evidence of craniosynostosis.…”

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confidence: 99%

“…Interstitial tandem duplication of 6p; the involvement of RUNX2 and IL17F genes could explain the phenotype [Bart et al, 2011;Varvagiannis et al, 2013]. 1 M 6p12.3 and 6p21.1p22.2/18q21.32 Gruchy et al, 2010 46,XY,der(18)(18pter→18q21.32::6p22.2→6p21.1::6p12.3→ 6p12.3::18q21.32→18qter)pat; complex chromosomal rearrangement; A, B, L, hypotonia, and deafness.…”

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confidence: 99%

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Karyotype-Phenotype Correlation in Partial Trisomies of the Short Arm of Chromosome 6: A Family Case Report and Review of the Literature

Castiglione

Guaran

Astolfi

et al. 2013

Cytogenet Genome Res

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The first child (proband) of nonconsanguineous Caucasian parents underwent genetic investigation because she was affected with congenital choanal atresia, heart defects and kidney hyposplasia with mild transient renal insufficiency. The direct DNA sequencing after PCR of the CHD7 gene, which is thought to be responsible for approximately 60-70% of the cases of CHARGE syndrome/association, found no mutations. The cytogenetic analysis (standard GTG banding karyotype) revealed the presence of extrachromosomal material on 10q. The chromosome analysis was completed with array CGH (30 kb resolution), MLPA and FISH, which allowed the identification of three 6p regions (6p.25.3p23 × 3): 2 of these regions are normally located on chromosome 6, and the third region is translocated to the long arm of chromosome 10. The same chromosomal rearrangement was subsequently found in the father, who was affected with congenital ptosis and progressive hearing loss, and in the proband's sister, the second child, who presented at birth with choanal atresia and congenital heart defects. The mutated karyotypes, which were directly inherited, are thought to be responsible for a variable phenotype, including craniofacial dysmorphisms, choanal atresia, congenital ptosis, sensorineural hearing loss, heart defects, developmental delay, and renal dysfunction. Nevertheless, to achieve a complete audiological assessment of the father, he underwent further investigation that revealed an increased level of the coagulation factor XIII (300% increased activity), fluctuating levels of fibrin D-dimer degradation products (from 296 to 1,587 ng/ml) and a homoplasmic mitochondrial DNA mutation: T961G in the MTRNR1 (12S rRNA) gene. He was made a candidate for cochlear implantation. Preoperative high-resolution computed tomography and magnetic resonance imaging of the temporal bone revealed the presence of an Arnold-Chiari malformation type I. To the best of our knowledge, this study is the second report on partial 6p trisomy that involves the 10q terminal region. Furthermore, we report the first case of documented Arnold-Chiari malformation type I and increased factor XIII activity associated with 6p trisomy. We present a comprehensive report of the familial cases and an exhaustive literature review.

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Section: Discussionmentioning

confidence: 99%

Section: F 6p21pter/20p13mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Karyotype-Phenotype Correlation in Partial Trisomies of the Short Arm of Chromosome 6: A Family Case Report and Review of the Literature

Castiglione

Guaran

Astolfi

et al. 2013

Cytogenet Genome Res

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“…RUNX2 deficiency results in deficient skull ossification in the context of cleidocranial dysplasia. Importantly, RUNX2 duplication [Mefford et al, 2010], triplication [Varvagiannis et al, 2013] and quadruplication [Greives et al, 2013] have been reported in patients with syndromic CS and there appears to be a direct correlation between the gene copy number and the severity of the phenotype. Our group identified two rare missense variants, M175R and R237C in two of 137 patients with sNCS.…”

Section: Genetic Etiopathogenesis Of Craniosynostosismentioning

confidence: 99%

Genetic advances in craniosynostosis

Lattanzi

Barba

Pietro

et al. 2017

American J of Med Genetics Pt A

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Craniosynostosis, the premature ossification of one or more skull sutures, is a clinically and genetically heterogeneous congenital anomaly affecting approximately 1 in 2,500 live births. In most cases, it occurs as an isolated congenital anomaly, i.e. nonsyndromic craniosynostosis (NCS), the genetic and environmental causes of which remain largely unknown. Recent data suggest that at least some of the midline NCS cases may be explained by two loci inheritance. In approximately 25–30% of patients craniosynostosis presents as a feature of a genetic syndrome due to chromosomal defects or mutations in genes within interconnected signaling pathways. The aim of this review is to provide a detailed and comprehensive update on the genetic and environmental factors associated with NCS, integrating the scientific findings achieved during the last decade. Focus on the neurodevelopmental, imaging and treatment aspects of NCS is also provided.

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Molecular Genetics of Craniosynostosis

Lattanzi

2016

Encyclopedia of Life Sciences

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Craniosynostosis (CS) is a relatively prevalent congenital malformation, due to the premature ossification of calvarial sutures that articulate skull bones, leading to a variable alteration of craniofacial landmarks and shape. CS is extremely heterogeneous in both clinical and a etiological aspects. It occurs as an isolated defect (i.e. nonsyndromic) in most cases, while it is syndromic in less than one fourth of cases. A genetic aetiology (i.e. mutations in FGFR , TWIST1 , EFNB1 , MSX , and ERF genes, among others) is known for most syndromes. Recent studies helped clarifying the genetic basis of new CS syndromes and nonsyndromic forms. The discovery of new genes (including RUNX2 , ALX4 , TCF12 and ZIC1 ) enabled deciphering the complex signalling network that orchestrates craniofacial development. In this light, the entire CS disease spectrum can be regarded as a nosological continuum, with variable degree of severity, in which a strong genetic component provides the background for environmental factors that contribute to the aetiopathogenesis of the birth defect. Key Concepts Craniosynostosis is a frequent congenital defect with a high degree of clinical and genetic heterogeneity. Nonsyndromic forms are more frequent, although their aetiology is still poorly understood. Many developmental syndromes include craniosynostosis in their phenotype. Different closely interacting genes ( FGFR , TWIST1 , MSX2 , ERF , TCF12 , among others) are involved in the molecular genetics of the best characterised and more frequent syndromic craniosynostoses. Most genes involved in the etiopathogenesis of craniosynostosis interact within a common gene network.

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Pure de novo partial trisomy 6p in a girl with craniosynostosis

Cited by 20 publications

References 33 publications

Karyotype-Phenotype Correlation in Partial Trisomies of the Short Arm of Chromosome 6: A Family Case Report and Review of the Literature

Karyotype-Phenotype Correlation in Partial Trisomies of the Short Arm of Chromosome 6: A Family Case Report and Review of the Literature

Genetic advances in craniosynostosis

Molecular Genetics of Craniosynostosis

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