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Please use this identifier to cite or link to this item: http://acervodigital.unesp.br/handle/11449/18003
Title: 
Prevalence and nonrandom distribution of exonic mutations in interferon regulatory factor 6 in 307 families with Van der Woude syndrome and 37 families with popliteal pterygium syndrome
Author(s): 
Institution: 
  • Universidade Estadual Paulista (UNESP)
  • Univ Iowa
  • Univ Catholique Louvain
  • Univ Pittsburgh
  • GeneDx
  • Univ Regensburg
  • University of Manchester
  • Hop Jean Flandre
  • Clin Univ St Luc
  • Universidade de São Paulo (USP)
ISSN: 
1098-3600
Sponsorship: 
  • NIH
  • Fonds Speciaux de Recherche-Universite catholique de Louvain
  • Fonds de la Recherche Scientifique (FNRS)
  • F.R.I.A. (Fonds pour la formation a la recherche dans l'industrie et dans l'agriculture)
Sponsorship Process Number: 
  • NIH: R01-DE013513
  • NIH: R01-DE08559
  • NIH: P50-DE016215
Abstract: 
Purpose: Interferon regulatory factor 6 encodes a member of the IRF family of transcription factors. Mutations in interferon regulatory factor 6 cause Van der Woude and popliteal pterygium syndrome, two related orofacial clefting disorders. Here, we compared and contrasted the frequency and distribution of exonic Mutations in interferon regulatory factor 6 between two large geographically distinct collections of families with Van der Woude and between one collection of families with popliteal pterygium syndrome. Methods: We performed direct sequence analysis of interferon regulatory factor 6 exons oil samples from three collections, two with Van der Woude and one with popliteal pterygium syndrome. Results: We identified mutations in interferon regulatory factor 6 exons in 68% of families in both Van der Woude collections and in 97% of families with popliteal pterygium syndrome. In sum, 106 novel disease-causing variants were found. The distribution of mutations in the interferon regulatory factor 6 exons in each collection was not random; exons 3, 4, 7, and 9 accounted for 80%. In the Van der Woude collections, the mutations were evenly divided between protein truncation and missense, whereas most mutations identified in the popliteal pterygium syndrome collection were missense. Further, the missense mutations associated with popliteal pterygium syndrome were localized significantly to exon 4, at residues that are predicted to bind directly to DNA. Conclusion: The nonrandom distribution of mutations in the interferon regulatory factor 6 exons suggests a two-tier approach for efficient mutation screens for interferon regulatory factor 6. The type and distribution of mutations are consistent with the hypothesis that Van der Woude is caused by haploinsufficiency of interferon regulatory factor 6. Oil the other hand, the distribution of popliteal pterygium syndrome-associated mutations suggests a different, though not mutually exclusive, effect oil interferon regulatory factor 6 function. Genet Med 2009:11(4):241-247.
Issue Date: 
1-Apr-2009
Citation: 
Genetics In Medicine. Philadelphia: Lippincott Williams & Wilkins, v. 11, n. 4, p. 241-247, 2009.
Time Duration: 
241-247
Publisher: 
Lippincott Williams & Wilkins
Keywords: 
  • cleft lip and palate
  • mutation
  • haploinsufficiency
  • dominant negative
  • cryptic splice site
  • CpG
Source: 
http://dx.doi.org/10.1097/GIM.0b013e318197a49a
URI: 
Access Rights: 
Acesso restrito
Type: 
outro
Source:
http://repositorio.unesp.br/handle/11449/18003
Appears in Collections:Artigos, TCCs, Teses e Dissertações da Unesp

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