Analysis Of Relevant Pathogenic Regions In Patients With Congenital Heart Disease And Chromosome Abnormality

Congenital heart disease(CHD) is the most common type of birth defect. CHD often occurs in association with other birth malformations. 25% of children with CHD and additional malformations had abnormal copy number changes, therefore, it is vey important to confirm the pathogenesis of chromosome abnormality for improving survival rate and the quality of life. Objective To identify the deletions or duplications regions of chromosome and screen for pathogenic genes which conform with clinical features. To explore the correlation between the candidate genes and the phenotype.Methods We have collected two patients from two families. To identify the chromosome abnormality and copy number variations, we investigated the probands by karyotyping, Agilent CGH Array?Affymetrix Cyto Scan HD and real-time PCR. Furthermore, we used whole exome sequencing to detect the gene mutations. According to the database of OMIM and Pubmed, relavant candidate genes related with clinical characteristic were selected.Results 1. Karyotyping of the members in the two family showed abnormalities, 46,XX,del(9)(q31.1q32) and 45,XY,der(13) t(13; 18)(p12; q11.2), respectively. 2. Results of Agilent CGH Array 4×180K showed a deletion of 9q31.1-q32(105190105-117195154), and the deletion length is 12.01 Mb. Results of Affymetrix Cyto Scan HD Assay demonstrated a deletion of 18p11.32-q11.1(136226-18529578), the deletion length is 18.393 Mb. 3. q PCR showed that patient 1 carried SMC2?CTNNAL1 and DFBN31 gene deletion, and patient 2 carried TYMS and TGIF1 gene deletion. 4. Whole exome sequencing demonstrated that patient 1 did not carry candidate gene mutations, such as NIPBL?SMC1A?SMC3?MRPS22 ?RAD21and HDAC8 gene.Conclusion 1. In this study, we identified two deletion regions of two chromosome abnormalities patients by karyotyping, Agilent CGH Array, Cyto Scan HD and whole exome sequencing, and selected several genes which is related to some clinical features. 2. The comparison of our patient with 11 previously reported cases with partially overlapping deletions showed similar phenotypes, and these phenotypes are similar to those of Cd LS. 3. In this study, we first link SMC2 gene and Cd L syndrome. 4. We speculated the cardiac phenotype is correlated with TYMS gene in 18 p chromosome deletion.