Most of the cases are sporadic. Several mutations in the OFD1 gene have been described to date and include frameshifts, splicing, missense, non-sense, in-frame deletions, and genomic rearrangements although the majority is represented by frameshift mutations. Mutations in the OFD1 transcripts have also been reported in X-linked recessive Joubert cases (JBS10) an X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction, in X-linked recessive retinitis pigmentosa (RP23) and in patients displaying primary ciliary dyskinesia (PCD). The mutations at least in OFD type I syndrome are predicted to act with a loss of function mechanism. Molecular testing is available and recommended when the diagnosis is suspected. The diagnosis relies on sequencing of the coding regions and dosage analysis of negative cases (females) to detect genomic rearrangements.
OFD1