KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes

Audrey Putoux, Sophie Thomas, Karlien L.M. Coene, Erica Ellen Davis, Yasemin Alanay, Gönöl Ogur, Elif Uz, Daniela Buzas, Céline Gomes, Sophie Patrier, Christopher L. Bennett, Nadia Elkhartoufi, Marie Hélène Saint Frison, Luc Rigonnot, Nicole Joyé, Solenn Pruvost, Gulen Eda Utine, Koray Boduroglu, Patrick Nitschke, Laura FertittaChristel Thauvin-Robinet, Arnold Munnich, Valérie Cormier-Daire, Raoul Hennekam, Estelle Colin, Nurten Ayse Akarsu, Christine Bole-Feysot, Nicolas Cagnard, Alain Schmitt, Nicolas Goudin, Stanislas Lyonnet, Férechté Encha-Razavi, Jean Pierre Siffroi, Mark Winey, Elias Nicholas Katsanis, Marie Gonzales, Michel Vekemans, Philip L. Beales, Tania Attié-Bitach*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

172 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)601-606
Number of pages6
JournalNature Genetics
Issue number6
StatePublished - Jun 2011

ASJC Scopus subject areas

  • Genetics


Dive into the research topics of 'KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes'. Together they form a unique fingerprint.

Cite this