CCDC151 Recessive Loss-of-Function Mutations in Three Families with Primary Ciliary Dyskinesia and Situs Inversus
(A) Pedigree structure and segregation analysis in PCD families carrying CCDC151 mutations showing an inheritance pattern consistent with disease status, as indicated by presence of the mutant or normal (WT) alleles. Consanguineous unions OP and UCL-65 share the same mutation, c.925G>T. Asterisks indicate situs inversus; double lines indicate first-degree consanguinity.
(B) Representative sequence traces (top) for the two CCDC151 homozygous nonsense mutations detected in affected individuals. The examples are amplified from individual OP-675 (c.925G>T) predicting a premature termination of translation p.Glu309∗ and individual 71154 II:2 (c.1256C>A) predicting a premature termination of translation p.Ser419∗. The normal (WT) sequence is shown below.
(C) Chest X-ray of individual OP-675 shows situs inversus totalis; R indicates right side.
(D) The location of mutations within the intron-exon structure of CCDC151 is shown above: black and white boxes indicate the coding exons, gray the 5′ and 3′ UTRs. Below, the location of the mutations is shown within the corresponding 595-amino-acid CCDC151 protein (RefSeq NP_659482.3) model, predicted using SMART. Green boxes indicate coiled-coil domains; yellow boxes indicate low-complexity repeat regions.