NIPBL Mutational Analysis in 120 Individuals with Cornelia de Lange Syndrome and Evaluation of Genotype-Phenotype Correlations
The American Journal of Human GeneticsPublished 12 September 2004Open access
Lynette A. Gillis, Jennifer McCallum, Maninder Kaur, Cheryl DeScipio, Dinah Yaeger, Allison Mariani
Citations317
SJR quartileQ1
SJR score4.53
SNIP2.47
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TL;DR
The spectrum and distribution of NIPBL mutations in a large well-characterized cohort of individuals with Cornelia de Lange syndrome suggested a trend toward a milder phenotype in individuals with missense mutations than in those with other types of mutations.
Abstract
The Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder characterized by facial dysmorphia, upper-extremity malformations, hirsutism, cardiac defects, growth and cognitive retardation, and gastrointestinal abnormalities. Both missense and protein-truncating mutations in NIPBL, the human homolog of the Drosophila melanogaster Nipped-B gene, have recently been reported to cause CdLS. The function of NIPBL in mammals is unknown. The Drosophila Nipped-B protein facilitates long-range enhancer-promoter interactions and plays a role in Notch signaling and other developmental pathways, as well as being involved in mitotic sister-chromatid cohesion. We report the spectrum and distribution of NIPBL mutations in a large well-characterized cohort of individuals with CdLS. Mutations were found in 56 (47%) of 120 unrelated individuals with sporadic or familial CdLS. Statistically significant phenotypic differences between mutation-positive and mutation-negative individuals were identified. Analysis also suggested a trend toward a milder phenotype in individuals with missense mutations than in those with other types of mutations.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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