Mutations and variants in the cohesion factor genes NIPBL, SMC1A, and SMC3 in a cohort of 30 unrelated patients with Cornelia de Lange syndrome.

Am J Med Genet A 2010 Apr;152A(4):924-9

Laboratory of Clinical Genetics and Functional Genomics, Department of Pharmacology, Medical School, University of Zaragoza, Zaragoza, Spain.

Cornelia de Lange syndrome (CdLS) manifests facial dysmorphic features, growth and cognitive impairment, and limb malformations. Mutations in three genes (NIPBL, SMC1A, and SMC3) of the cohesin complex and its regulators have been found in affected patients. Here, we present clinical and molecular characterization of 30 unrelated patients with CdLS. Eleven patients had mutations in NIPBL (37%) and three patients had mutations in SMC1A (10%), giving an overall rate of mutations of 47%. Several patients shared the same mutation in NIPBL (p.R827GfsX2) but had variable phenotypes, indicating the influence of modifiers in CdLS. Patients with NIPBL mutations had a more severe phenotype than those with mutations in SMC1A or those without identified mutations. However, a high incidence of palate defects was noted in patients with SMC1A mutations. In addition, we observed a similar phenotype in both male and female patients with SMC1A mutations. Finally, we report the first patient with an SMC1A mutation and the Sandifer complex.

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.33348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923429PMC
April 2010

Publication Analysis

Top Keywords

mutations
10
patients
9
mutations smc1a
8
smc1a smc3
8
smc1a mutations
8
patients smc1a
8
lange syndrome
8
cornelia lange
8
nipbl smc1a
8
unrelated patients
8
patients mutations
8
genes nipbl
8
smc1a
7
nipbl
5
mutation nipbl
4
shared mutation
4
patients shared
4
nipbl pr827gfsx2
4
variable phenotypes
4
influence modifiers
4

Similar Publications