DNAH11 compound heterozygous variants cause heterotaxy and congenital heart disease

• Published in: PloS one Vol. 16; no. 6; p. e0252786
• Main Authors: Xia, Hong, Huang, Xiangjun, Deng, Sheng, Xu, Hongbo, Yang, Yan, Liu, Xin, Yuan, Lamei, Deng, Hao
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.06.2021; Public Library of Science (PLoS)
• Subjects: Analysis; Asian People - genetics; Axonemal Dyneins - chemistry; Axonemal Dyneins - genetics; Biology and Life Sciences; Cardiovascular disease; Cardiovascular diseases; Child, Preschool; China; Chloroform; Congenital diseases; Coronary artery disease; Cyanosis; Data analysis; Deoxyribonucleic acid; DNA; DNA sequencing; Dynein; Dyspnea; Editing; Electronic mail; Emergency medical services; Exome Sequencing - methods; Families & family life; Female; Funding; Gene sequencing; Genes; Genetic aspects; Genetic Predisposition to Disease - ethnology; Genetic Predisposition to Disease - genetics; Genomes; Genotype & phenotype; Heart Defects, Congenital - ethnology; Heart Defects, Congenital - genetics; Heart Defects, Congenital - pathology; Heart diseases; Herbal medicine; Heterotaxy Syndrome - ethnology; Heterotaxy Syndrome - genetics; Heterotaxy Syndrome - pathology; Heterozygosity; Heterozygote; Hospitals; Humans; Male; Medicine; Medicine and Health Sciences; Methodology; Mutation; Mutation, Missense; Neurology; Nucleotide sequencing; Organs; Pedigree; People and Places; Phenols; Phenotype; Point mutation; Protein Conformation; Proteins; Research and analysis methods; Reviews; Rhinitis; Surgery; Vertebrates; Visualization; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0252786

Heterotaxy (HTX), a condition characterized by internal organs not being arranged as expected relative to each other and to the left-right axis, is often accompanied with congenital heart disease (CHD). The purpose was to detect the pathogenic variants in a Chinese family with HTX and CHD. A non-consanguineous Han Chinese family with HTX and CHD, and 200 unrelated healthy subjects were enlisted. Exome sequencing and Sanger sequencing were applied to identify the genetic basis of the HTX family. Compound heterozygous variants, c.3426-1G>A and c.4306C>T (p.(Arg1436Trp)), in the dynein axonemal heavy chain 11 gene ( DNAH11 ) were identified in the proband via exome sequencing and further confirmed by Sanger sequencing. Neither c.3426-1G>A nor c.4306C>T variant in the DNAH11 gene was detected in 200 healthy controls. The DNAH11 c.3426-1G>A variant was predicted as altering the acceptor splice site and most likely affecting splicing. The DNAH11 c.4306C>T variant was predicted to be damaging, which may reduce the phenotype severity. The compound heterozygous variants, c.3426-1G>A and c.4306C>T, in the DNAH11 gene might be the pathogenic alterations resulting in HTX and CHD in this family. These findings broaden the variant spectrum of the DNAH11 gene and increase knowledge used in genetic counseling for the HTX family.