title: C5orf42 is the major gene responsible for OFD syndrome type VI.
abstract: 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.
authors.affiliation: Equipe d'accueil EA 4271 GAD "Génétique des Anomalies du Développement", IFR Santé STIC, Université de Bourgogne, Dijon, France, estl_l@yahoo.fr.
authors.forename: Estelle
authors.initials: E
authors.lastname: Lopez
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.forename: Bruno
authors.initials: B
authors.lastname: Reversade
authors.forename: Nadia El
authors.initials: NE
authors.lastname: Khartoufi
authors.forename: Louise
authors.initials: L
authors.lastname: Devisme
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder
authors.forename: Hélène
authors.initials: H
authors.lastname: Ansart-Franquet
authors.forename: Magali
authors.initials: M
authors.lastname: Avila
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Pascale
authors.initials: P
authors.lastname: Kleinfinger
authors.forename: Irahara
authors.initials: I
authors.lastname: Kaori
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Takanashi
authors.forename: Martine
authors.initials: M
authors.lastname: Le Merrer
authors.forename: Jelena
authors.initials: J
authors.lastname: Martinovic
authors.forename: Catherine
authors.initials: C
authors.lastname: Noël
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shboul
authors.forename: Lena
authors.initials: L
authors.lastname: Ho
authors.forename: Yeliz
authors.initials: Y
authors.lastname: Güven
authors.forename: Ferechté
authors.initials: F
authors.lastname: Razavi
authors.forename: Lydie
authors.initials: L
authors.lastname: Burglen
authors.forename: Nadège
authors.initials: N
authors.lastname: Gigot
authors.forename: Véronique
authors.initials: V
authors.lastname: Darmency-Stamboul
authors.forename: Julien
authors.initials: J
authors.lastname: Thevenon
authors.forename: Bernard
authors.initials: B
authors.lastname: Aral
authors.forename: Hülya
authors.initials: H
authors.lastname: Kayserili
authors.forename: Frédéric
authors.initials: F
authors.lastname: Huet
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Cédric
authors.initials: C
authors.lastname: Le Caignec
authors.forename: Brunella
authors.initials: B
authors.lastname: Franco
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Rivière
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Tania
authors.initials: T
authors.lastname: Attié-Bitach
mesh_terms: D000015:Abnormalities, Multiple; D000293:Adolescent; D000328:Adult; D000483:Alleles; D002526:Cerebellar Diseases / Q000175:diagnosis / Q000235:genetics; D002531:Cerebellum / Q000002:abnormalities; D002648:Child; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D059472:Exome; D005124:Eye Abnormalities / Q000175:diagnosis / Q000235:genetics; D005260:Female; D006222:Hamartoma / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007027:Hypothalamic Diseases / Q000175:diagnosis / Q000235:genetics; D052177:Kidney Diseases, Cystic / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009421:Nervous System Malformations / Q000175:diagnosis / Q000235:genetics; D009958:Orofaciodigital Syndromes / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D017689:Polydactyly / Q000175:diagnosis / Q000235:genetics; D012160:Retina / Q000002:abnormalities; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: C572460:CPLANE1 protein, human; D008565:Membrane Proteins