From a single whole exome read to notions of clinical screening: primary ciliary dyskinesia and RSPH9 p.Lys268del in the Arabian Peninsula.

摘要: Primary ciliary dyskinesia (PCD) is a genetic disorder, usually autosomal recessive, causing early respiratory disease and later subfertility. Whole exome sequencing may enable efficient analysis for locus heterogeneous disorders such as PCD. We whole-exome-sequenced one consanguineous Saudi Arabian with clinically diagnosed PCD normal laterality, to attempt ab initio molecular diagnosis. reviewed 13 known genes potentially autozygous regions (extended homozygosity) homozygous exon deletions, non-dbSNP codon, splice-site base variants or small indels. Homozygous changes were also exome-wide. One single read representing RSPH9 p.Lys268del was observed, no wild-type reads, notable deficiency of mapped reads at this location. Among all observations, the strongest candidate causality. Searching unmapped revealed seven more mutant reads. Direct assay (MboII digest) confirmed homozygosity in affected individual, then three siblings bronchiectasis. Our finding southwest Arabia indicates that p.Lys268del, previously observed two Bedouin families (Israel, UAE), geographically widespread Peninsula. Analogous cystic fibrosis CFTR p.Phe508del, screening (which lacks sentinel dextrocardia) those risk would help diagnosis, tailored clinical management, counselling primary prevention.