Identification of TCTE3 as a gene responsible for congenital diaphragmatic hernia using a high-resolution single-nucleotide polymorphism array

• DOI: 10.1007/s00383-010-2778-z
• Publication Date: 2010-11-16T23:39:19Z
• Authors: Risa Teshiba; Kouji Masumoto; Genshiro Esumi; Kouji Nagata; Yoshiaki Kinoshita; Tatsuro Tajiri; Tomoaki Taguchi; Ken Yamamoto
• Keywords: Cytoplasmic Dyneins; Hernia, Diaphragmatic; 0301 basic medicine; Dyneins; DNA; Polymorphism, Single Nucleotide; 3. Good health; 03 medical and health sciences; Gene Expression Regulation; Humans; Genetic Predisposition to Disease; Hernias, Diaphragmatic, Congenital

Congenital diaphragmatic hernia (CDH) is a birth defect of the diaphragm associated with pulmonary hypoplasia. Although genetic factors have been suggested to play a role, the etiology of CDH is still largely unknown. In this study, we analyzed copy number variants (CNVs) using a single-nucleotide polymorphism (SNP) array to examine whether microdeletions contribute to the pathogenesis of this disease.A total of 28 CDH patients, including 24 isolated and 4 non-isolated cases, were available. We performed CNV analysis using high-resolution SNP arrays (370K, 550K, 660K; Illumina Inc.) and CNstream software. Deletions in loci that have been suggested in previous studies to contain candidate genes affecting CDH were analyzed.We detected 335, 6 and 133 deletions specific for patients in 14 (350K array), 3 (550K) and 11 (660K) cases, respectively. Among these deletions, no segments included the previously suggested candidate genes with the exception of an 18-kb deletion observed in the candidate locus 6q27 in two non-isolated patients. This deleted region contains exon 4 of the t-complex-associated-testis-expressed 3 (TCTE3) gene.Because TCTE3 encodes a putative light chain of the outer dynein arm of cilia and human diseases caused by ciliary dysfunction show various phenotypes including skeletal defect, TCTE3 may be a genetic candidate influencing CDH.