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KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes.

Authors: Putoux, A  Thomas, S  Coene, KL  Davis, EE  Alanay, Y  Ogur, G  Uz, E  Buzas, D  Gomes, C  Patrier, S  Bennett, CL  Elkhartoufi, N  Frison, MH  Rigonnot, L  Joye, 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, JP  Winey, M  Katsanis, N  Gonzales, M  Vekemans, M  Beales, PL  Attie-Bitach, T 
Citation: Putoux A, etal., Nat Genet. 2011 Jun;43(6):601-6. doi: 10.1038/ng.826. Epub 2011 May 8.
Pubmed: (View Article at PubMed) PMID:21552264
DOI: Full-text: DOI:10.1038/ng.826

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.


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CRRD Object Information
CRRD ID: 11068757
Created: 2016-04-27
Species: All species
Last Modified: 2016-04-27
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.