Weiguo Sui1, Xianliang Hou1,2, Wenti Che1, Minglin Ou1, Guoping Sun3, Shengxing Huang4, Fuhua Liu1, Peng Chen1, Xiaolian Wei1, Yong Dai5,6. 1. Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi, China. 2. College of Life Science, Guangxi Normal University, Guilin, Guangxi, China. 3. Lab. Center, Shenzhen Pingshan People's Hospital, Shenzhen, Guangdong, China. 4. Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China. 5. Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi, China. daiyong2222@gmail.com. 6. Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China. daiyong2222@gmail.com.
Abstract
BACKGROUND AND AIMS: 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.
BACKGROUND AND AIMS: 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: Raymond C Pasek; Erik Malarkey; Nicolas F Berbari; Neeraj Sharma; Robert A Kesterson; Laura L Tres; Abraham L Kierszenbaum; Bradley K Yoder Journal: Dev Biol Date: 2016-03-03 Impact factor: 3.582