中国循证儿科杂志2016，Vol.11Issue(6)：445-449,5.DOI:10.3969/j.issn.1673-5501.2016.06.009
CCDC39基因突变致原发性纤毛运动障碍1例及其遗传咨询和产前诊断
Genetic counseling and prenatal diagnosis for primary ciliary dyskinesia in a case caused by CCDC39 gene mutations
摘要
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 Childrenˊs 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.关键词
原发性纤毛运动障碍/全外显子组测序/遗传咨询/产前诊断Key words
Primary ciliary dyskinesia/Whole exome sequencing/Genetic counseling/Prenatal diagnosis引用本文复制引用
祁媛媛,洪达,王慧君,张晓波,王立波,金婷婷,钱莉玲..CCDC39基因突变致原发性纤毛运动障碍1例及其遗传咨询和产前诊断[J].中国循证儿科杂志,2016,11(6):445-449,5.基金项目
上海市科委西医引导项目134119a7800、14411962102；上海市人才发展基金沪人201450 （）
