ABSTRACT
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.
Subject(s)
Axonemal Dyneins/genetics , Genetic Predisposition to Disease/genetics , Heart Defects, Congenital/genetics , Heterotaxy Syndrome/genetics , Mutation, Missense , Asian People/genetics , Axonemal Dyneins/chemistry , Child, Preschool , China , Female , Genetic Predisposition to Disease/ethnology , Heart Defects, Congenital/ethnology , Heart Defects, Congenital/pathology , Heterotaxy Syndrome/ethnology , Heterotaxy Syndrome/pathology , Heterozygote , Humans , Male , Pedigree , Phenotype , Protein Conformation , Exome Sequencing/methodsABSTRACT
We retrospectively analyzed a combination of prenatally detected and postnatally diagnosed patients with heterotaxic situs that included those with situs inversus, bilateral left-sidedness, and bilateral right-sidedness for the period between April 2002 and July 2014. We found a statistically higher prevalence in the Hispanic population of Southern Nevada of 2.7/10,000 live births (95 % confidence intervals of 1.7-3.9) versus the non-Hispanic population of 1.6/10,000 live births (95 % confidence intervals of 1.1-2.1), p = 0.04. Additionally, we noted a high prenatal detection rate of 68 % over the 12-year period of time, rising to 100 % over the last 2 years.
