C5orf42 is the major gene responsible for OFD syndrome type VI

Estelle Lopez, Christel Thauvin-Robinet, Bruno Reversade, Nadia El Khartoufi, Louise Devisme, Muriel Holder, Hélène Ansart-Franquet, Magali Avila, Didier Lacombe, Pascale Kleinfinger, Irahara Kaori, Jun Ichi Takanashi, Martine Le Merrer, Jelena Martinovic, Catherine Noël, Mohammad Shboul, Lena Ho, Yeliz Güven, Ferechté Razavi, Lydie BurglenNadège Gigot, Véronique Darmency-Stamboul, Julien Thevenon, Bernard Aral, Hülya Kayserili, Frédéric Huet, Stanislas Lyonnet, Cédric Le Caignec, Brunella Franco, Jean Baptiste Rivière, Laurence Faivre, Tania Attié-Bitach

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Oral-facial-digital syndrome type VI (OFD VI) is a recessive ciliopathy defined by two diagnostic criteria: molar tooth sign (MTS) and one or more of the following: (1) tongue hamartoma (s) and/or additional frenula and/or upper lip notch; (2) mesoaxial polydactyly of one or more hands or feet; (3) hypothalamic hamartoma. Because of the MTS, OFD VI belongs to the "Joubert syndrome related disorders". Its genetic aetiology remains largely unknown although mutations in the TMEM216 gene, responsible for Joubert (JBS2) and Meckel-Gruber (MKS2) syndromes, have been reported in two OFD VI patients. To explore the molecular cause(s) of OFD VI syndrome, we used an exome sequencing strategy in six unrelated families followed by Sanger sequencing. We identified a total of 14 novel mutations in the C5orf42 gene in 9/11 families with positive OFD VI diagnostic criteria including a severe fetal case with microphthalmia, cerebellar hypoplasia, corpus callosum agenesis, polydactyly and skeletal dysplasia. C5orf42 mutations have already been reported in Joubert syndrome confirming that OFD VI and JBS are allelic disorders, thus enhancing our knowledge of the complex, highly heterogeneous nature of ciliopathies. © 2013 Springer-Verlag Berlin Heidelberg.
Original languageEnglish (US)
Pages (from-to)367-377
Number of pages11
JournalHuman Genetics
Issue number3
StatePublished - Mar 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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