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Journal article
SMC1A Expression and Mechanism of Pathogenicity in Probands with X-linked Cornelia de Lange Syndrome
Human mutation, v 30(11), pp 1535-1542
01 Nov 2009
PMID: 19701948
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Cornelia de Lange Syndrome (CdLS) is a dominantly inherited heterogeneous genetic disorder with multi-system abnormalities. 60% of probands with CdLS have heterozygous mutations in the
Nipped-B- like
(
NIPBL
) gene, 5% have mutations in the
SMC1A
gene, and 1 proband was found to have a mutation in the
SMC3
gene. Cohesin is a multi-subunit complex consisting of a SMC1A and SMC3 heterodimer and two non-SMC subunits.
SMC1A
is located on the human X chromosome and is reported to escape X inactivation. We show that 29 unrelated CdLS probands with 21 unique
SMC1A
mutations have been identified by our group and others including 7 males. All mutations identified to date are either missense or small deletions with all presumably preserving the protein open reading frame. Both wild type and mutant alleles are expressed. Females quantitatively express twice the amount of
SMC1A
mRNA as compared to males. The transcriptional profiling of 23 selected genes is different in
SMC1A
mutant probands, controls and
NIPBL
mutant probands. These results suggest that mechanistically
SMC1A
-related CdLS is not due to altered levels of the
SMC1A
transcript, but rather that the mutant proteins maintain a residual function in males and enact a dominant negative effect in females.
Metrics
Details
- Title
- SMC1A Expression and Mechanism of Pathogenicity in Probands with X-linked Cornelia de Lange Syndrome
- Creators
- Jinglan Liu - Children's Hospital of PhiladelphiaRachel Feldman - Children's Hospital of PhiladelphiaZhe Zhang - Children's Hospital of PhiladelphiaMatthew A. Deardorff - Children's Hospital of PhiladelphiaEden V. Haverfield - University of ChicagoManinder Kaur - Children's Hospital of PhiladelphiaJennifer R. Li - Children's Hospital of PhiladelphiaDinah Clark - Children's Hospital of PhiladelphiaAntonie D. Kline - Greater Baltimore Medical CenterDarrel J. Waggoner - University of ChicagoSoma Das - University of ChicagoLaird G. Jackson - Drexel UniversityIan D. Krantz - University of Pennsylvania
- Publication Details
- Human mutation, v 30(11), pp 1535-1542
- Publisher
- Wiley
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pathology (and Laboratory Medicine)
- Web of Science ID
- WOS:000271576600005
- Scopus ID
- 2-s2.0-70350702802
- Other Identifier
- 991019350683904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Genetics & Heredity