Oral‑facial‑digital syndrome type VI: is C5orf42 really the major gene?

Oral-facial-digital type VI syndrome (OFDVI) is a rare phenotype of Joubert syndrome(JS). Recently, C5orf42 was suggested as the major OFDVI gene, being mutatedin 9 of 11 families (82 %). We sequenced C5orf42 in 313 JS probandsand identified mutationsin 28 (8.9 %), most with a phenotype of pure JS. Only 2 out of 17 OFDVI patients (11.7 %) were mutated. A comparison of mutatedvs. non- mutatedOFDVI patients showed that preaxial and mesoaxial polydactyly, hypothalamic hamartomaand other congenital defects may predict C5orf42 mutations, while tongue hamartomasare more common in negative patients.