PP26 A GENOTYPE-PHENOTYPE CORRELATION OF PRIMARY CILIARY DYSKINESIA (PCD) DUE TO CCNO MUTATIONS

Mariana Daud
Hospital Raja Perempuan Zainab11, Kota Bharu, Malaysia

Objective:

Primary ciliary dyskinesia (PCD) is a rare inherited autosomal recessive with heterogenous manifestations. There are over 50 mutated genes in PCD.CCNO mutations are considered rare, but there are reports that suggest otherwise. CCNO mutations are associated with chronic destructive lung disease with worse lung outcomes. The purpose of this study was to clarify the clinical profile of genetically confirmed PCD patients due to CCNO mutations and examine the genotype-phenotype correlation. 

Methods:

A retrospective chart review of confirmed PCD patients by Whole Exon Sequencing (WES) (done at 3billion Laboratory, South Korea from October 2021 to December 2021) that were seen at Paediatric Respiratory Clinic, Hospital Raja Perempuan Zainab 11 Kelantan.  

Results:

Four patients (4/7, 57.1%) were diagnosed with PCD due to CCNO mutations and 50% are male. Two of them are biological siblings (NP_066970.3:p.Leu303CysfsTer24  homozygous mutation) and one of the patients is their niece (NP_066970.3:p.Leu303CysfsTer24  heterozygous and NP_066970.3:p.Gly85CysfsTer 11 heterozygous). Interestingly, these three relatives have high total IgE levels (1854 to >5,000 kU/L). The other patient has NP_066970.3:p.Gly85CysfsTer 11 homozygous mutation. Age at diagnosis was between 1 to 24 years (mean, 13.5 years). The mean interval from diagnosis of Bronchiectasis to confirmed PCD was 85.25 months (2-162 months). All (100%) had recurrent respiratory infections with confirmed bronchiectasis (100%) and perennial rhinitis (100%). One patient has an advanced stage of bronchiectasis, dependent on home ventilation and oxygen therapy. Aural symptoms were present in 25%. None had situs inversus or congenital cardiac anomalies. The mean PICADAR score was 6. The mean Nasal nitric Oxide (nNO) level was 19.7 ppb. The mean of the first FEV1/FVC was 73.7 (range 60-94), first FEV1 45.3 (range 36-50) and first FVC was 55.7 (range 45-72). 

Conclusion:

CCNO mutations are the commonest mutated genes in Malaysian PCD patients. The affected patients have significant respiratory limitations and respiratory morbidity. Interestingly, certain CCNO mutations are associated with hyperimmunoglobulin E that needs further research