The majority of cases are sporadic. Several mutations in the OFD1 gene have been described to date and include mutations affecting single nucleotides (frameshifts, splicing, missense, non-sense, in-frame deletions), and genomic mutations involving a larger portion of the gene. However, the majority of mutations is represented by frameshift mutations. Mutations in the OFD1 transcripts have also been reported in different genetic conditions: 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 is based on sequencing of the coding regions (including sites involved in splicing) and dosage analysis of negative cases (females) to detect genomic rearrangements.
OFD1