Clinical Domain Working Groups

The goal of the Motile Ciliopathy Gene Curation Expert Panel is to classify the clinical validity of gene-disease relationships involving primary ciliary dyskinesia (PCD) and related disorders of the motile cilia.

There are difficulties in PCD genetics diagnosis hence the need for ClinGen based gene curation. As for any of the ciliopathies, PCD manifests as a variable penetrance/expressivity multisystem disease. There are no direct diagnostic tests and an increasing reliance on being able to do reliable genetic testing and interpretation, especially as diagnosis widens out to centres that lack specialised cilia functional equipment and expertise such as high speed video, electron microscopy, immunofluorescence testing. It is currently accepted that there are around 50 PCD-causing genes. Current NGS methods can diagnose around 70% of PCD cases with causal mutations, hence we expect more PCD genes to emerge and indeed there are regular new publications with increasingly smaller patient numbers and harder to interpret gene variants as the major players such as DNAH5, DNAH11 have probably been defined already VSports app下载.

The expert team聽we have gathered together have extensive knowledge about this variable penetrance/expressivity multisystem disease, but much remains unknown about genotype-phenotype relationships. It is known that certain PCD genes are excluded from causing certain disease features, e V体育官网. g. known subsets of genes do not cause laterality defects, hydrocephalus or male infertility. Further, data are emerging on differences in severity of airway disease, according to gene, e. g. DNAH9 causes a milder airway disease expression, patients with CCDC103 H154P mutations can often show up normal cilia tests. Our aim is to support genetic testing, increasing its reliability for implementation into diagnostics, for better detection/diagnosis of PCD worldwide.