NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations

被引:249
作者
Gillis, LA
McCallum, J
Kaur, M
DeScipio, C
Yaeger, D
Mariani, A
Kline, AD
Li, HH
Devoto, M
Jackson, LG
Krantz, ID
机构
[1] Childrens Hosp Philadelphia, Div Human & Mol Genet, Abramson Res Ctr 1002, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Philadelphia, PA 19104 USA
[3] Drexel Univ, Sch Med, Div Obstet & Gynecol, Philadelphia, PA 19104 USA
[4] Vanderbilt Univ, Med Ctr, Div Gastroenterol, Nashville, TN USA
[5] Vanderbilt Univ, Med Ctr, Div Genet, Nashville, TN USA
[6] Greater Baltimore Med Ctr, Harvey Inst Human Genet, Baltimore, MD USA
[7] Nemours Childrens Clin, Wilmington, DE USA
[8] Univ Genoa, Dept Biol Oncol & Genet, Genoa, Italy
关键词
D O I
10.1086/424698
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:610 / 623
页数:14
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