@entity910 ( @entity910 ) is a genetically heterogeneous @entity74 arising from @entity4423 of motile cilia and sperm. This is associated with a variety of ultrastructural defects of the cilia and sperm axoneme that affect movement, leading to clinical consequences on respiratory-tract mucociliary clearance and lung function, fertility, and left-right body- @entity2270 determination. We performed whole-genome SNP-based linkage analysis in seven consanguineous families with @entity910 and central-microtubular-pair abnormalities. This identified two loci, in two families with intermittent absence of the central-pair structure (chromosome 6p21.1, Zmax 6.7) and in five families with complete absence of the central pair (chromosome 6q22.1, Zmax 7.0). Mutations were subsequently identified in two positional candidate genes, @entity70263 on chromosome 6p21.1 and @entity70264 on chromosome 6q22.1. Haplotype analysis identified a common ancestral founder effect @entity70264 mutation present in UK-Pakistani pedigrees. Both @entity70263 and @entity70264 encode protein components of the axonemal radial spoke head. In situ hybridization of @entity19 @entity70265 shows gene expression restricted to regions containing motile cilia. Investigation of the effect of knockdown or mutations of @entity70263 orthologs in @entity3392 and Chlamydomonas indicate that radial spoke head proteins are important in maintaining normal movement in motile, "9+2"-structure cilia and flagella. This effect is rescued by reintroduction of gene expression for restoration of a normal beat pattern in @entity3392 . Disturbance in function of these genes was not associated with defects in @entity2270 in @entity1 or @entity3392 .

Mutations in radial spoke head protein genes XXXX and @entity70264 cause primary @entity910 with central-microtubular-pair abnormalities.

@entity1 :: ('9606', 'Species') :: ['humans'] @entity19 :: ('10090', 'Species') :: ['murine'] @entity910 :: ('MESH:D004409', 'Disease') :: ['PCD', 'Primary ciliary dyskinesia'] @entity70263 :: ('558005(Tax:7955)', 'Gene') :: ['RSPH9'] @entity70265 :: ('75564(Tax:10090)', 'Gene') :: ['Rsph9'] @entity70264 :: ('335497(Tax:7955)', 'Gene') :: ['RSPH4A'] @entity74 :: ('MESH:D030342', 'Disease') :: ['inherited disorder'] @entity2270 :: ('MESH:C566610', 'Disease') :: ['left-right axis determination', 'axis'] @entity4423 :: ('MESH:D015154', 'Disease') :: ['dysmotility'] @entity3392 :: ('7955', 'Species') :: ['zebrafish']
@entity70263 :: (558005(Tax:7955),Gene) :: ['RSPH9']
