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  Cranioectodermal Dysplasia, Sensenbrenner syndrome, is a ciliopathy caused by mutations in the IFT122 gene.

Walczak-Sztulpa, J., Eggenschwiler, J., Osborn, D., Brown, D. A., Emma, F., Klingenberg, C., et al. (2010). Cranioectodermal Dysplasia, Sensenbrenner syndrome, is a ciliopathy caused by mutations in the IFT122 gene. American Journal of Human Genetics, 86(6), 949-956. doi:10.1016/j.ajhg.2010.04.012.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7AD3-4 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7AD4-2
Genre: Journal Article
Alternative Title : Am. J. Hum. Genet.

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 Creators:
Walczak-Sztulpa, Joanna1, Author
Eggenschwiler, Jonathan, Author
Osborn, Daniel, Author
Brown, Desmond A., Author
Emma, Francesco, Author
Klingenberg, Claus, Author
Hennekam, Raoul C., Author
Torre, Giuliano, Author
Garshasbi, Masoud2, Author              
Tzschach, Andreas2, Author              
Szczepanska, Malgorzata, Author
Krawczynski, Marian, Author
Zachwieja, Jacek, Author
Zwolinska, Danuta, Author
Beales, Philip L., Author
Ropers, Hans-Hilger2, Author              
Latos-Bielenska, Anna, Author
Kuss, Andreas W.3, Author              
Affiliations:
1Max Planck Society, ou_persistent13              
2Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              
3Familial Cognitive Disorders (Luciana Musante), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479644              

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 Abstract: Cranioectodermal dysplasia (CED) is a disorder characterized by craniofacial, skeletal, and ectodermal abnormalities. Most cases reported to date are sporadic, but a few familial cases support an autosomal-recessive inheritance pattern. Aiming at the elucidation of the genetic basis of CED, we collected 13 patients with CED symptoms from 12 independent families. In one family with consanguineous parents two siblings were affected, permitting linkage analysis and homozygosity mapping. This revealed a single region of homozygosity with a significant LOD score (3.57) on chromosome 3q21-3q24. By sequencing candidate genes from this interval we found a homozygous missense mutation in the IFT122 (WDR10) gene that cosegregated with the disease. Examination of IFT122 in our patient cohort revealed one additional homozygous missense change in the patient from a second consanguineous family. In addition, we found compound heterozygosity for a donor splice-site change and a missense change in one sporadic patient. All mutations were absent in 340 control chromosomes. Because IFT122 plays an important role in the assembly and maintenance of eukaryotic cilia, we investigated patient fibroblasts and found significantly reduced frequency and length of primary cilia as compared to controls. Furthermore, we transiently knocked down ift122 in zebrafish embryos and observed the typical phenotype found in other models of ciliopathies. Because not all of our patients harbored mutations in IFT122, CED seems to be genetically heterogeneous. Still, by identifying CED as a ciliary disorder, our study suggests that the causative mutations in the unresolved cases most likely affect primary cilia function too.

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Language(s): eng - English
 Dates: 2010-06-11
 Publication Status: Published in print
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Title: American Journal of Human Genetics
  Alternative Title : Am. J. Hum. Genet.
Source Genre: Journal
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Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 86 (6) Sequence Number: - Start / End Page: 949 - 956 Identifier: ISSN: 0002-9297