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Comprehensive mutational analysis of a cohort of Swedish Cornelia de Lange syndrome patients

Schoumans, Jacqueline ; Wincent, Josephine ; Barbaro, Michela ; Djureinovic, Tatjana ; Maguire, Paula ; Forsberg, Lena ; Staaf, Johan LU orcid ; Thuresson, Ann Charlotte ; Borg, Åke LU and Nordgren, Ann , et al. (2007) In European Journal of Human Genetics 15(2). p.143-149
Abstract
Cornelia de Lange syndrome (CdLS; OMIM 122470) is a rare multiple congenital anomaly/mental retardation syndrome characterized by distinctive dysmorphic facial features, severe growth and developmental delay and abnormalities of the upper limbs. About 50% of CdLS patients have been found to have heterozygous mutations in the NIPBL gene and a few cases were recently found to be caused by mutations in the X-linked SMC1L1 gene. We performed a mutation screening of all NIPBL coding exons by direct sequencing in 11 patients ( nine sporadic and two familial cases) diagnosed with CdLS in Sweden and detected mutations in seven of the cases. All were de novo, and six of the mutations have not been previously described. Four patients without... (More)
Cornelia de Lange syndrome (CdLS; OMIM 122470) is a rare multiple congenital anomaly/mental retardation syndrome characterized by distinctive dysmorphic facial features, severe growth and developmental delay and abnormalities of the upper limbs. About 50% of CdLS patients have been found to have heterozygous mutations in the NIPBL gene and a few cases were recently found to be caused by mutations in the X-linked SMC1L1 gene. We performed a mutation screening of all NIPBL coding exons by direct sequencing in 11 patients ( nine sporadic and two familial cases) diagnosed with CdLS in Sweden and detected mutations in seven of the cases. All were de novo, and six of the mutations have not been previously described. Four patients without identifiable NIPBL mutations were subsequently subjected to multiplex ligation-dependent probe amplification analysis to exclude whole exon deletions/duplications of NIPBL. In addition, mutation analysis of the 50 untranslated region (5' UTR) of NIPBL was performed. Tiling resolution array comparative genomic hybridization analysis was carried out on these four patients to detect cryptic chromosome imbalances and in addition the boys were screened for SMC1L1 mutations. We found a de novo 9p duplication with a size of 0.6Mb in one of the patients with a CdLS-like phenotype but no mutations were detected in SMC1L1. So far, two genes ( NIPBL and SMC1L1) have been identified causing CdLS or CdLS-like phenotypes. However, in a considerable proportion of individuals demonstrating the CdLS phenotype, mutations in any of these two genes are not found and other potential loci harboring additional CdLS-causing genes should be considered. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
chromosome, array-CGH, mutation, Cornelia de Lange syndrome, NIPBL, abnormalities, SMC1L1
in
European Journal of Human Genetics
volume
15
issue
2
pages
143 - 149
publisher
Nature Publishing Group
external identifiers
  • wos:000243565600004
  • scopus:33846300688
ISSN
1476-5438
DOI
10.1038/sj.ejhg.5201737
language
English
LU publication?
yes
id
398a8fa6-6974-4aa2-a608-063832e511c4 (old id 676679)
date added to LUP
2016-04-01 12:33:18
date last changed
2022-04-13 20:33:32
@article{398a8fa6-6974-4aa2-a608-063832e511c4,
  abstract     = {{Cornelia de Lange syndrome (CdLS; OMIM 122470) is a rare multiple congenital anomaly/mental retardation syndrome characterized by distinctive dysmorphic facial features, severe growth and developmental delay and abnormalities of the upper limbs. About 50% of CdLS patients have been found to have heterozygous mutations in the NIPBL gene and a few cases were recently found to be caused by mutations in the X-linked SMC1L1 gene. We performed a mutation screening of all NIPBL coding exons by direct sequencing in 11 patients ( nine sporadic and two familial cases) diagnosed with CdLS in Sweden and detected mutations in seven of the cases. All were de novo, and six of the mutations have not been previously described. Four patients without identifiable NIPBL mutations were subsequently subjected to multiplex ligation-dependent probe amplification analysis to exclude whole exon deletions/duplications of NIPBL. In addition, mutation analysis of the 50 untranslated region (5' UTR) of NIPBL was performed. Tiling resolution array comparative genomic hybridization analysis was carried out on these four patients to detect cryptic chromosome imbalances and in addition the boys were screened for SMC1L1 mutations. We found a de novo 9p duplication with a size of 0.6Mb in one of the patients with a CdLS-like phenotype but no mutations were detected in SMC1L1. So far, two genes ( NIPBL and SMC1L1) have been identified causing CdLS or CdLS-like phenotypes. However, in a considerable proportion of individuals demonstrating the CdLS phenotype, mutations in any of these two genes are not found and other potential loci harboring additional CdLS-causing genes should be considered.}},
  author       = {{Schoumans, Jacqueline and Wincent, Josephine and Barbaro, Michela and Djureinovic, Tatjana and Maguire, Paula and Forsberg, Lena and Staaf, Johan and Thuresson, Ann Charlotte and Borg, Åke and Nordgren, Ann and Malm, Gunilla and Anderlid, Britt Marie}},
  issn         = {{1476-5438}},
  keywords     = {{chromosome; array-CGH; mutation; Cornelia de Lange syndrome; NIPBL; abnormalities; SMC1L1}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{143--149}},
  publisher    = {{Nature Publishing Group}},
  series       = {{European Journal of Human Genetics}},
  title        = {{Comprehensive mutational analysis of a cohort of Swedish Cornelia de Lange syndrome patients}},
  url          = {{http://dx.doi.org/10.1038/sj.ejhg.5201737}},
  doi          = {{10.1038/sj.ejhg.5201737}},
  volume       = {{15}},
  year         = {{2007}},
}