C5orf42 is the major gene responsible for OFD syndrome type VI.

Hum Genet 2014 Mar 1;133(3):367-77. Epub 2013 Nov 1.

Equipe d'accueil EA 4271 GAD "Génétique des Anomalies du Développement", IFR Santé STIC, Université de Bourgogne, Dijon, France,

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.

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http://dx.doi.org/10.1007/s00439-013-1385-1DOI Listing
March 2014
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References

(Supplied by CrossRef)

IA Adzhubei et al.
Nat Methods 2010

AM Alazami et al.
Human mutation 2012

IJ Bisschoff et al.
Hum Mutat 2013

F Brancati et al.
Orphanet J Rare Dis 2010

M Chaki et al.
Cell 2012

KL Coene et al.
Am J Hum Genet 2009

MA DePristo et al.
Nat Genet 2011

BJ Doss et al.
Am J Med Genet 1998

LE Figuera et al.
Clin Genet 1993

JG Gleeson et al.
Am J Med Genet A 2004

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