Investigate On Cilia Ultrastructurals And Genotype Of Primary Ciliary Dyskinesia

Background:Primary ciliary dyskinesia(PCD)is a rare inherited disease which including autosomal recessive inherited,X-linked inherited and some are unidentified yet.It’s ability of cilia mucus removal injured because of cilia ultrastructure defects and/or movement disorder.The etiology of PCD is "9 + 2" motile cilia,mainly distributes in the upper and lower respiratory tract,eustachian tube,ependyma,fallopian tube,sperm flagella and so on.The clinical symptoms are decided by the affected organs.The clinical features are chronic sinusitis,recurrent respiratory tract infections,bronchiectasis,otitis media,maleinfertility and female fertility,of which half combined with situs inversus are called Kartagener syndrome.The assistant examinations of PCD are varied,like Imaging features,nasal nitric oxide,high-speed digital video imaging,transmission electron microscopy and genetic testing.But none of them is "gold standard".Genetic testing united with other examinations have significant value on early and accuracy of diagnosis.The type of gene mutation is related to its ciliary unltrastructure defect.Majority of researches about gene mutation of PCD are in Europe and America populations.Whether the molecular genetic characteristics of PCD in Chinese are differences with westerners are unclear.Objective:Cilia ultrastructures and genetic mutation features of primary ciliary dyskinesia are investigated.Analyse the association between genotype-phenotypeMethod:Clinical informations and gene mutations of 4 PCD children who were diagnosed by transmission electron microscopy in xx hospital between 2013 and 2016 was analyzed.Target gene sequence capture and next generation sequencing were used to detect gene.Related literature about gene mutation of Chinese PCD was reviewed from Online Mendelian Inheritance in Man(OMIM),Human Gene Mutation Database(HGMD),Pubmed and CNKI.Summarize the association between genetic defects and ciliary ultrastructure.Result:(1)There were one male and three females aged from 3 to 11 years.The common symptoms included:recurrent productive cough starting soon after birth,sinusitis,bronchiectasis.Two of them had situs inversus.(2)Transmission electron microscopy of the endobronchial biopsy showed lack of outer and inner dynein arms in 1 and 2,abnormality in microtubule and inner dynein arms in 3 and 4.Gene mutation was detected in 3 of 4 PCD patients,which contained compound heterozygous mutation of LRRC6,heterozygous mutations on DNAH5 and DNAH11,homozygous mutation on CCDC39.The above mutations have not been reported.The forth patient complicated with cystic fibrosis caused by CFTR genetic mutation.(3)The studies about gene mutation of PCD in Chinese focused on Kartagener syndrome patients.There are 7 cases have positive gene testing and 6 of them are Kartagener syndrome.The genotype-phenotype correlation structure is consistent with previous reports.Conclusion:Patients with recurrent respiratory infection since childhood,chest CT showed bronchiectasis or diffuse panbronchiolitis,treatment for recurrent wheezing and coughing was ineffective,PCD should be considered.There seems to be a clear association between ciliary ultrastructure defects and genotype.Genetic testing has a certain application value in the diagnosis of PCD.The genetic diagnosis of propositus provides guiding significance on genetic counseling and prenatal diagnosis for PCD family.