Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Left-sided congenital heart disease (CHD) encompasses a spectrum of malformations that range from bicuspid aortic valve to hypoplastic left heart syndrome. It contributes significantly to infant mortality and has serious implications in adult cardiology. Although left-sided CHD is known to be highly heritable, the underlying genetic determinants are largely unidentified. In this study, we sought to determine the impact of structural genomic variation on left-sided CHD and compared multiplex families (464 individuals with 174 affecteds (37.5%) in 59 multiplex families and 8 trios) to 1,582 well-phenotyped controls. 73 unique inherited or de novo CNVs in 54 individuals were identified in the left-sided CHD cohort. After stringent filtering, our gene inventory reveals 25 new candidates for LS-CHD pathogenesis, such as SMC1A, MFAP4, and CTHRC1, and overlaps with several known syndromic loci. Conservative estimation examining the overlap of the prioritized gene content with CNVs present only in affected individuals in our cohort implies a strong effect for unique CNVs in at least 10% of left-sided CHD cases. Enrichment testing of gene content in all identified CNVs showed a significant association with angiogenesis. In this first family-based CNV study of left-sided CHD, we found that both co-segregating and de novo events associate with disease in a complex fashion at structural genomic level. Often viewed as an anatomically circumscript disease, a subset of left-sided CHD may in fact reflect more general genetic perturbations of angiogenesis and/or vascular biology.
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PMID:Rare copy number variants contribute to congenital left-sided heart disease. 2296 34

Both children (one boy and one girl) experienced disease onset in infancy and visited the hospital due to growth retardation. They had unusual facies including thick hair, arched and confluent eyebrows, long and curly eyelashes, short nose, and micrognathia. Patient 1 had congenital heart disease (atrial septal defect and pulmonary stenosis) and special dermatoglyph (a single palmar crease). Patient 2 had cleft palate and moderate-to-severe deafness. Clinical features suggested Cornelia de Lange syndrome in both children. High-throughput sequencing was used to detect the seven known pathogenic genes of Cornelia de Lange syndrome, i.e., the NIPBL, SMC1A, SMC3, HDAC8, RAD21, EP300, and ANKRD11 genes. Sanger sequencing was used to analyze and verify gene mutations. Both patients were found to have novel mutations in the NIPBL gene. One patient had a frameshift mutation in exon 45, c.7834dupA, which caused early termination of translation and produced truncated protein p.R2612fsX20. The other patient had a nonsense mutation, c.505C>T, which caused a premature stop codon and produced truncated protein Q169X. Such mutations were not found in their parents or 50 unrelated healthy individuals.
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PMID:[NIPBL gene mutations in two children with Cornelia de Lange syndrome]. 2976 76