title: CCDC40 mutation as a cause of primary ciliary dyskinesia: a case report and review of literature.
abstract: OBJECTIVE
  Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder. Genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, situs inversus and, frequently, male infertility in PCD. To date, although several genes have been implicated in PCD, the genetic bases of most cases of PCD remain elusive.
  
  
  METHODS
  By applying a whole-exome sequencing strategy, we reported a case of PCD carrying a novel mutant alleles in CCDC40 gene, and did literature review.
  
  
  RESULTS
  A 36-year-old nonsmoking Chinese man suffered from chronic cough since childhood and an 8-year history of primary infertility. Lung biopsy showed respiratory bronchiolitis. Chest images showed bronchiectasis and situs inversus. Semen analysis showed high sperm counts and poor sperm motility. Transmission electron microscopy (TEM) of cilia cross-sections showed ultrastructural defects, including inner dynein arms (IDA) defect and axonemal disorganization. To identify gene mutations that cause PCD, we performed exome sequencing to analyze genome of this patient, and discovered a previously uncharacterized mutant alleles (NM_001243342.1:c.2609G>A; p. R870H) in CCDC40 gene. In addition, we summarize the PCD disease-causing genes and CCDC40 mutant sites based on current literature.
  
  
  CONCLUSIONS
  We identified a novel mutant alleles in CCDC40 gene, which altered the protein sequence and resulted in the ultrastructural defects in the microtubule structure of cilia. Thereby, these defects lead to the patient with bronchiectasis, bronchiolitis and infertility.
authors.affiliation: Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Sui
authors.affiliation: Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi, China.|College of Life Science, Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Xianliang
authors.initials: X
authors.lastname: Hou
authors.affiliation: Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi, China.
authors.forename: Wenti
authors.initials: W
authors.lastname: Che
authors.affiliation: Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi, China.
authors.forename: Minglin
authors.initials: M
authors.lastname: Ou
authors.affiliation: Lab. Center, Shenzhen Pingshan People's Hospital, Shenzhen, Guangdong, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Sun
authors.affiliation: Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
authors.forename: Shengxing
authors.initials: S
authors.lastname: Huang
authors.affiliation: Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi, China.
authors.forename: Fuhua
authors.initials: F
authors.lastname: Liu
authors.affiliation: Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi, China.
authors.forename: Xiaolian
authors.initials: X
authors.lastname: Wei
authors.affiliation: Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi, China. daiyong2222@gmail.com.|Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China. daiyong2222@gmail.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000328:Adult; D059472:Exome; D020022:Genetic Predisposition to Disease; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D007619:Kartagener Syndrome / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
chemical_list: C556028:CCDC40 protein, human; D011506:Proteins
keywords: exome sequencing; mutation; primary ciliary dyskinesia; respiratory bronchiolitis; situs inversus