High rate of mosaicism in individuals with Cornelia de Lange syndrome
- PMID: 23505322
- DOI: 10.1136/jmedgenet-2012-101477
High rate of mosaicism in individuals with Cornelia de Lange syndrome
Abstract
Background: Cornelia de Lange syndrome (CdLS) is a well known malformation syndrome for which five causative genes are known, accounting for ∼55-65% of cases. In this study, we hypothesised that mosaicism might explain some of the ∼35-45% of cases without detectable mutation in DNA derived from lymphocytes; we investigated the frequency of NIPBL mutations in buccal cells in individuals negative for mutations in any of the five genes in lymphocytes; and we evaluated the efficiency of obtaining DNA from buccal swabs and the best strategy for optimal mutation detection in CdLS.
Methods: Buccal swabs were obtained from eight mutation positive and 13 mutation negative individuals with clinically diagnosed CdLS, following informed consent. We then forwarded instructions and a single mouth swab to the families; if subsequently insufficient DNA was obtained, we re-sent two mouth swabs. Buccal cells were screened for NIPBL mutations using Sanger sequencing techniques.
Results: Sufficient DNA for analysis was obtained in 21/22 individuals. In all six tested individuals with a known NIPBL mutation and in two with a known SMC1A mutation, the mutation was confirmed in buccal cells. In 10 of the 13 tested individuals without detectable mutation in lymphocytes a NIPBL mutation could be detected in buccal cells. Clinically there were no significant differences between patients with a germline and mosaic NIPBL mutation.
Conclusions: Somatic mosaicism for an NIPBL mutation is frequent (10/44; 23%) clinically in reliably diagnosed CdLS individuals. Obtaining buccal swabs at the time a blood sample is obtained will facilitate adequate molecular analysis of clinically diagnosed CdLS patients.
Similar articles
-
Molecular characterization of a mosaic NIPBL deletion in a Cornelia de Lange patient with severe phenotype.Eur J Med Genet. 2013 Mar;56(3):138-43. doi: 10.1016/j.ejmg.2012.12.009. Epub 2013 Jan 8. Eur J Med Genet. 2013. PMID: 23313159
-
Comprehensive mutational analysis of a cohort of Swedish Cornelia de Lange syndrome patients.Eur J Hum Genet. 2007 Feb;15(2):143-9. doi: 10.1038/sj.ejhg.5201737. Epub 2006 Nov 15. Eur J Hum Genet. 2007. PMID: 17106445
-
A novel mosaic variant on SMC1A reported in buccal mucosa cells, albeit not in blood, of a patient with Cornelia de Lange-like presentation.Cold Spring Harb Mol Case Stud. 2020 Jun 12;6(3):a005322. doi: 10.1101/mcs.a005322. Print 2020 Jun. Cold Spring Harb Mol Case Stud. 2020. PMID: 32532882 Free PMC article.
-
Cornelia de Lange syndrome.Clin Genet. 2015 Jul;88(1):1-12. doi: 10.1111/cge.12499. Epub 2014 Oct 28. Clin Genet. 2015. PMID: 25209348 Review.
-
Mutation spectrum and genotype-phenotype correlation in Cornelia de Lange syndrome.Hum Mutat. 2013 Dec;34(12):1589-96. doi: 10.1002/humu.22430. Epub 2013 Sep 16. Hum Mutat. 2013. PMID: 24038889 Free PMC article. Review.
Cited by
-
Identification of two novel heterozygous variants of SMC3 with Cornelia de Lange syndrome.Mol Genet Genomic Med. 2024 May;12(5):e2447. doi: 10.1002/mgg3.2447. Mol Genet Genomic Med. 2024. PMID: 38733165 Free PMC article.
-
Advancing the Clinical and Molecular Understanding of Cornelia de Lange Syndrome: A Multidisciplinary Pediatric Case Series and Review of the Literature.J Clin Med. 2024 Apr 21;13(8):2423. doi: 10.3390/jcm13082423. J Clin Med. 2024. PMID: 38673696 Free PMC article. Review.
-
Human embryonic genetic mosaicism and its effects on development and disease.Nat Rev Genet. 2024 Apr 11. doi: 10.1038/s41576-024-00715-z. Online ahead of print. Nat Rev Genet. 2024. PMID: 38605218 Review.
-
Long-read sequencing reveals chromothripsis in a molecularly unsolved case of Cornelia de Lange syndrome.Front Genet. 2024 Mar 13;15:1358334. doi: 10.3389/fgene.2024.1358334. eCollection 2024. Front Genet. 2024. PMID: 38544803 Free PMC article.
-
Comprehensive review and expanding the genetic landscape of Cornelia-de-Lange spectrum: insights from novel mutations and skin biopsy in exome-negative cases.BMC Med Genomics. 2024 Jan 12;17(1):20. doi: 10.1186/s12920-024-01798-7. BMC Med Genomics. 2024. PMID: 38216990 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials