KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes.


Journal Article

KIF7, the human ortholog of Drosophila Costal2, is a key component of the Hedgehog signaling pathway. Here we report mutations in KIF7 in individuals with hydrolethalus and acrocallosal syndromes, two multiple malformation disorders with overlapping features that include polydactyly, brain abnormalities and cleft palate. Consistent with a role of KIF7 in Hedgehog signaling, we show deregulation of most GLI transcription factor targets and impaired GLI3 processing in tissues from individuals with KIF7 mutations. KIF7 is also a likely contributor of alleles across the ciliopathy spectrum, as sequencing of a diverse cohort identified several missense mutations detrimental to protein function. In addition, in vivo genetic interaction studies indicated that knockdown of KIF7 could exacerbate the phenotype induced by knockdown of other ciliopathy transcripts. Our data show the role of KIF7 in human primary cilia, especially in the Hedgehog pathway through the regulation of GLI targets, and expand the clinical spectrum of ciliopathies.

Full Text

Cited Authors

  • Putoux, A; Thomas, S; Coene, KLM; Davis, EE; Alanay, Y; Ogur, G; Uz, E; Buzas, D; Gomes, C; Patrier, S; Bennett, CL; Elkhartoufi, N; Frison, M-HS; Rigonnot, L; Joyé, N; Pruvost, S; Utine, GE; Boduroglu, K; Nitschke, P; Fertitta, L; Thauvin-Robinet, C; Munnich, A; Cormier-Daire, V; Hennekam, R; Colin, E; Akarsu, NA; Bole-Feysot, C; Cagnard, N; Schmitt, A; Goudin, N; Lyonnet, S; Encha-Razavi, F; Siffroi, J-P; Winey, M; Katsanis, N; Gonzales, M; Vekemans, M; Beales, PL; Attié-Bitach, T

Published Date

  • June 2011

Published In

Volume / Issue

  • 43 / 6

Start / End Page

  • 601 - 606

PubMed ID

  • 21552264

Pubmed Central ID

  • 21552264

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/ng.826


  • eng

Conference Location

  • United States