Precocious sister chromatid separation (PSCS) in Cornelia de Lange syndrome

Maninder Kaur, Cheryl DeScipio, Jennifer McCallum, Dinah Yaeger, Marcella Devoto, Laird G. Jackson, Nancy B. Spinner, Ian D. Krantz

Research output: Contribution to journalArticle

Abstract

The Cornelia de Lange syndrome (CdLS) (OMIM# 122470) is a dominantly inherited multisystem developmental disorder. The phenotype consists of characteristic facial features, hirsutism, abnormalities of the upper extremities ranging from subtle changes in the phalanges and metacarpal bones to oligodactyly and phocomelia, gastroesophageal dysfunction, growth retardation, and neurodevelopmental delay. Prevalence is estimated to be as high as 1 in 10,000. Recently, mutations in NIPBL were identified in sporadic and familial CdLS cases. To date, mutations in this gene have been identified in over 45% of individuals with CdLS. NIPBL is the human homolog of the Drosophila Nipped-B gene. Although its function in mammalian systems has not yet been elucidated, sequence homologs of Nipped-B in yeast (Scc2 and Mis4) are required for sister chromatid cohesion during mitosis, and a similar role was recently demonstrated for Nipped-B in Drosophila. In order to evaluate NIPBL role in sister chromatid cohesion in humans, metaphase spreads on 90 probands (40 NIPBL mutation positive and 50 NIPBL mutation negative) with CdLS were evaluated for evidence of precocious sister chromatid separation (PSCS). We screened 50 metaphases from each proband and found evidence of PSCS in 41% (compared to 9% in control samples). These studies indicate that NIPBL may play a role in sister chromatid cohesion in humans as has been reported for its homologs in Drosophila and yeast.

Original languageEnglish (US)
Pages (from-to)27-31
Number of pages5
JournalAmerican Journal of Medical Genetics
Volume138 A
Issue number1
DOIs
StatePublished - Sep 15 2005
Externally publishedYes

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Keywords

  • CdLS
  • Cornelia de Lange syndrome
  • NIPBL
  • Nipped-B
  • Precocious sister chromatid separation
  • PSCS

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Kaur, M., DeScipio, C., McCallum, J., Yaeger, D., Devoto, M., Jackson, L. G., Spinner, N. B., & Krantz, I. D. (2005). Precocious sister chromatid separation (PSCS) in Cornelia de Lange syndrome. American Journal of Medical Genetics, 138 A(1), 27-31. https://doi.org/10.1002/ajmg.a.30919