Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder caused 
by cilia and sperm dysmotility. About 12% of cases show perturbed 9+2 
microtubule cilia structure and inner dynein arm (IDA) loss, historically termed 
"radial spoke defect." We sequenced CCDC39 and CCDC40 in 54 "radial spoke 
defect" families, as these are the two genes identified so far to cause this 
defect. We discovered biallelic mutations in a remarkable 69% (37/54) of 
families, including identification of 25 (19 novel) mutant alleles (12 in CCDC39 
and 13 in CCDC40). All the mutations were nonsense, splice, and frameshift 
predicting early protein truncation, which suggests this defect is caused by 
"null" alleles conferring complete protein loss. Most families (73%; 27/37) had 
homozygous mutations, including families from outbred populations. A major 
putative hotspot mutation was identified, CCDC40 c.248delC, as well as several 
other possible hotspot mutations. Together, these findings highlight the key 
role of CCDC39 and CCDC40 in PCD with axonemal disorganization and IDA loss, and 
these genes represent major candidates for genetic testing in families affected 
by this ciliary phenotype. We show that radial spoke structures are largely 
intact in these patients and propose this ciliary ultrastructural abnormality be 
referred to as "IDA and microtubular disorganisation defect," rather than 
"radial spoke defect."