Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2004 Oct;75(4):610-23.
doi: 10.1086/424698. Epub 2004 Aug 18.

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

Lynette A Gillis  1 , Jennifer McCallum, Maninder Kaur, Cheryl DeScipio, Dinah Yaeger, Allison Mariani, Antonie D Kline, Hui-hua Li, Marcella Devoto, Laird G Jackson, Ian D Krantz
Affiliations
Comparative Study

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

Lynette A Gillis et al. Am J Hum Genet. 2004 Oct.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Facial features and limb findings in mutation-positive individuals with CdLS. Note the variability of features even among individuals with similar mutation types.
Figure 2
Figure 2
Evolutionary conservation of amino acid residues altered by missense mutations in NIPBL. A comparison of amino acids and the flanking sequence altered by 11 of the unique missense mutations in human (NIPBL), rat, mouse, and Drosophila is depicted. The mutated amino acid residue is shaded gray. Amino acid residue 2298 was mutated in three individuals—two had an R2298H change, and one had an R2298C change. The missense mutation M1K in the initiation codon is not depicted, since it is conserved in all species.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

Electronic-Database Information

    1. National Center for Biotechnology Information (NCBI),http://www.ncbi.nlm.nih.gov/ (for BAC RP11-14I21 [accession number AC018853.3])
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for CdLS) - PubMed

References

    1. Bankier A, Haan E, Birrell R (1986) Familial occurrence of Brachmann-de Lange syndrome. Am J Med Genet 25:163–165 - PubMed
    1. Beratis NG, Hsu LY, Hirschhorn K (1971) Familial de Lange syndrome: report of three cases in a sibship. Clin Genet 2:170–176 - PubMed
    1. Brachmann W (1916) Ein Fall von symmetrischer Monodaktylie durch Ulnadefekt, mit symmetrischer Flughautbildung in den Ellenbeugen, sowie anderen Abnormitäten (Zwerghaftigkeit, Halsrippen, Behaarung) [A case of symmetrical monodactyly representing ulnar deficiency, with symmetrical antecubital webbing and other abnormalities (dwarfish, cervical ribs, hirsutism)]. Jahrbuch für Kinderheilkunde und physische Erziehung 84:225–235
    1. Chodirker BN, Chudley AE (1994) Male-to-male transmission of mild Brachmann-de Lange syndrome. Am J Med Genet 52:331–333 - PubMed
    1. de Lange C (1933) Sur un type nouveau de dégénération (typus Amstelodamnesis) [On a new type of degeneration (type Amstelodamnesis)]. Arch Méd Enfants 36:713–719

Publication types

-