Deletion of 8p23.1 with features of Cornelia de Lange syndrome and congenital diaphragmatic hernia and a review of deletions of 8p23.1 to 8pter ? A further locus for Cornelia de Lange syndrome

Baynam, Gareth; Goldblatt, Jack; Walpole, Ian

doi:10.1002/ajmg.a.32095

Cited by 27 publications

(16 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the presence of genes whose products functionally overlap with those of known CdLS genes, further findings supporting the hypothesis that our probands are phenocopies of CdLS include: i) the localisation of the CEP170 gene which encodes a component of the centrosome [64], within a region (chromosome 1q44) shown to be deleted in a CdLS proband by Borck et al [11]; ii) the localisation of the TNKS gene, involved in sister chromatid cohesion, within the chromosome 8p23.1 region in the CdLS proband reported by Baynam et al [65]. …”

Section: Discussionsupporting

confidence: 87%

Genomic imbalances in patients with a clinical presentation in the spectrum of Cornelia de Lange syndrome

et al. 2013

View full text Add to dashboard Cite

BackgroundCornelia de Lange syndrome (CdLS) is a rare autosomal-dominant disorder characterised by facial dysmorphism, growth and psychomotor developmental delay and skeletal defects. To date, causative mutations in the NIPBL (cohesin regulator) and SMC1A (cohesin structural subunit) genes account for > 50% and 6% of cases, respectively.MethodsWe recruited 50 patients with a CdLS clinical diagnosis or with features that overlap with CdLS, who were negative for mutations at NIPBL and SMC1A at molecular screening. Chromosomal rearrangements accounting for the clinical diagnosis were screened for using array Comparative Genomic Hybridisation (aCGH).ResultsFour patients were shown to carry imbalances considered to be candidates for having pathogenic roles in their clinical phenotypes: patient 1 had a 4.2 Mb de novo deletion at chromosome 20q11.2-q12; patient 2 had a 4.8 Mb deletion at chromosome 1p36.23-36.22; patient 3 carried an unbalanced translocation, t(7;17), with a 14 Mb duplication of chromosome 17q24.2-25.3 and a 769 Kb deletion at chromosome 7p22.3; patient 4 had an 880 Kb duplication of chromosome 19p13.3, for which his mother, who had a mild phenotype, was also shown to be a mosaic.ConclusionsNotwithstanding the variability in size and gene content of the rearrangements comprising the four different imbalances, they all map to regions containing genes encoding factors involved in cell cycle progression or genome stability. These functional similarities, also exhibited by the known CdLS genes, may explain the phenotypic overlap between the patients included in this study and CdLS. Our findings point to the complexity of the clinical diagnosis of CdLS and confirm the existence of phenocopies, caused by imbalances affecting multiple genomic regions, comprising 8% of patients included in this study, who did not have mutations at NIPBL and SMC1A. Our results suggests that analysis by aCGH should be recommended for CdLS spectrum cases with an unexplained clinical phenotype and included in the flow chart for diagnosis of cases with a clinical evaluation in the CdLS spectrum.

show abstract

Section: Discussionsupporting

confidence: 87%

Genomic imbalances in patients with a clinical presentation in the spectrum of Cornelia de Lange syndrome

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The finding of an 8p deletion in one patient adds further evidence to this region being associated with CDH. 8p deletions encompassing the 8p23.1 microdeletion region have previously been observed in a number of patients with CDH (Pecile et al, 1990 , 1996;Faivre et al, 1998;Borys and Taxy, 2004;Shimokawa et al, 2005;Slavotinek et al, 2005;Lopez et al, 2006;Baynam et al, 2008;Wat et al, 2009). In addition, deletions of this region are also associated with congenital heart defects (Claeys et al, 1997;Devriendt et al, 1998Devriendt et al, , 1999.…”

Section: Discussionmentioning

confidence: 89%

Targeted array comparative genomic hybridisation (array CGH) identifies genomic imbalances associated with isolated congenital diaphragmatic hernia (CDH)

et al. 2010

View full text Add to dashboard Cite

Objective Congenital diaphragmatic hernia (CDH) is a congenital birth defect affecting around 1/3000 births. We propose that a significant number of isolated CDH cases have an underlying genetic cause, and that a subset of these result from copy number variations (CNVs) identifiable by array CGH. MethodologyWe have designed a custom array targeted at genes and genomic loci associated with CDH. A total of 79 isolated CDH patients were screened using this targeted array. ResultsIn three patients, we detected genomic imbalances associated with the observed diaphragmatic hernia; a deletion of 8p22-p23.3, 14.2 Mb in size, a 340 kb duplication of Xq13.1 including the ephrin-B1 gene (EFNB1 ), and mosaicism for trisomy 2.Conclusion Using this approach, we detected genomic imbalances associated with CDH in 3/79 (4%) isolated CDH patients. Our findings further implicate 8p deletions as being associated with CDH. The duplication of EFNB1 further highlights this gene as a potential candidate involved in diaphragm development. Mosaicism for trisomy 2 is a rare event and unlikely to be a common cause of CDH. Further investigations of isolated CDH patients by array CGH will continue to identify novel submicroscopic loci and refine genomic regions associated with CDH.

show abstract

“…These include the TRF1-interacting, ankyrin related ADP-ribose polymerase gene ( TNKS , OMIM*603303) for behavioural difficulties, and the SRY-Box 7 transcription factor ( SOX7 , OMIM *612202) for the developmental delay, as mutations of the related SOX3 gene have been associated with X-linked mental retardation [28]. By contrast, the diaphragmatic hernia found in a number of patients with the reciprocal deletion syndrome [29-31] has not, to our knowledge, been recorded in any 8p23.1 duplication syndrome patient to date.…”

Section: Discussionmentioning

confidence: 99%

8p23.1 duplication syndrome differentiated from copy number variation of the defensin cluster at prenatal diagnosis in four new families

et al. 2010

View full text Add to dashboard Cite

BackgroundThe 8p23.1 duplication syndrome and copy number variation of the 8p23.1 defensin gene cluster are cytogenetically indistinguishable but distinct at the molecular level. To our knowledge, the 8p23.1 duplication syndrome has been described at prenatal diagnosis only once and we report our experience with four further apparent duplications ascertained at prenatal diagnosis.MethodsAdditional material at band 8p23.1 was detected using conventional G-banded cytogenetics in each case. Multiplex Ligation-dependent Probe Amplification (MLPA) or Fluorescence In Situ Hybridisation (FISH) were used depending on whether only DNA (Cases 1 and 4) or cytogenetic preparations (Cases 2 and 3) were available from the laboratory of origin. The extent of the duplication in Case 1 was retrospectively determined using array Comparative Genomic Hybridisation (array CGH).ResultsThree cases of 8p23.1 duplication syndrome were found (Cases 1 to 3). Two were de novo and continued to term and the third, a paternally transmitted duplication, was terminated because of a previous child with psychomotor delay and 8p23.1 duplication syndrome. Case 1 was ascertained with a hypoplastic left heart but the ventricular septal and interventricular defects, in Cases 2 and 3 respectively, were found after ascertainment for advanced maternal age. By contrast, case 4 was a maternally transmitted copy number variation of the defensin cluster with normal outcome.ConclusionsOur data underline the need to differentiate 8p23.1 duplications from copy number variation of the defensin cluster using FISH, MLPA or array CGH. Cardiac defects were ascertained by ultrasound in only one of the three duplication 8p23.1 pregnancies but were visible in two of the three at 21 to 22 weeks gestation. Our results provide further evidence that both deletion and duplication of the GATA4 transcription factor can give rise to a variety of conotruncal heart defects with variable penetrance and expressivity.

show abstract

Deletion of 8p23.1 with features of Cornelia de Lange syndrome and congenital diaphragmatic hernia and a review of deletions of 8p23.1 to 8pter ? A further locus for Cornelia de Lange syndrome

Cited by 27 publications

References 30 publications

Genomic imbalances in patients with a clinical presentation in the spectrum of Cornelia de Lange syndrome

Genomic imbalances in patients with a clinical presentation in the spectrum of Cornelia de Lange syndrome

Targeted array comparative genomic hybridisation (array CGH) identifies genomic imbalances associated with isolated congenital diaphragmatic hernia (CDH)

8p23.1 duplication syndrome differentiated from copy number variation of the defensin cluster at prenatal diagnosis in four new families

Contact Info

Product

Resources

About