Abstract:

Objective To identify the genetic defect in a child with primary ciliary dyskinesia and provide genetic counseling and prenatal diagnosis for the family. Methods Whole exome sequencing (WES) was performed in a case with a clinical diagnosis of Kartagener syndrome as well as her asymptomatic parents. The data analysis pipeline of Children's Hospital of Fudan University was used to identify pathogenic mutations. Amniocentesis was conducted for the mother in her second pregnancy after a thorough genetic counseling. Genomic DNA was extracted from exfoliated amniotic fluid cells and Sanger sequencing was performed after PCR amplification. Results During follow-ups, the lung function of the patient deteriorated markedly and bronchiectasis shown in chest CT was aggravated. A heterozygous nonsense mutation (c.1819A>A/T, p.K607X) and a frameshift mutation (c.2447_2448het_delCA, p.T816Kfs*3) in CCDC39 gene were detected in this patient by WES. Both mutations were novel and predicted to be disease-causing. Mutational analysis of the parents demonstrated they were compound heterozygous mutations. These compound heterozygous mutations were consistent with ciliary structural abnormity revealed by electron microscope thus suggesting the pathogenic nature of these mutations. Sequencing of the amniotic fluid cells showed that the fetus only carried one heterozygous mutation which was inherited from the mother. Conclusion The compound heterozygous mutations in CCDC39 gene detected by WES was the genetic cause of primary ciliary dyskinesia. Genetic counseling and prenatal diagnosis may be helpful to the family based on the basis of this genetic diagnosis.