To develop an approach based on next-generation sequencing to determine the genetic defects in ciliopathies precisely and effectively.

Six suspected cases of ciliopathies were enrolled from July 2009 to December 2014 in the PLA General Hospital. Cord blood or tissue of the probands and peripheral blood samples of all the parents were collected for karyotyping analysis. Tissue or blood DNA from the six cases was scanned on 113 kinds of genes related to ciliopathies using targeted exome capture with high throughput sequencing. Mutations detected from the related genes were confirmed by direct Sanger sequencing reactions.

Karyotype was normal in all the six cases. Pathogenic genes were found in five cases, including PKHD1 mutation in two cases (case one with c.6091delG and c.865delC, and case two with c.11042T>G and c.5137G>T); TCTN2 mutation in one case (c.343G>T and c.1540C>T) and CEP290 mutation in one case (c.7328_7332del and c.4897C>T). All were compound heterozygous mutations. TMEM67 mutation was found in one case (c.1645C>T), which was homozygous mutation. First-generation sequencing confirmed that these mutations originated from their parents. No definite pathogenic courses were found in one case (case six).

Targeted exome capture with high throughput sequencing is a new approach to find pathogenic gene mutations in ciliopathies. The methodology provides a reliable strategy for routine gene diagnosis and genetic counseling on ciliopathies.

Polycystic kidney, autosomal recessive; Ciliary motility disorders; Encephalocele; Abnormalities, multiple; Exons; High-throughput nucleotide sequencing