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- Title
Genetic Analyses Identified a <italic>SALL4</italic> Gene Mutation Associated with Holt–Oram Syndrome.
- Authors
Li, Bojian; Chen, Sun; Sun, Kun; Xu, Rang; Wu, Yurong
- Abstract
Holt–Oram syndrome (HOS) is an autosomal dominant disorder, which is characterized by deformities of upper limbs and congenital heart defects. Alterations of <italic>TBX5</italic> gene have been identified to be the leading cause of HOS, while some cases could not be explained by <italic>TBX5</italic> mutations. In our study, we preliminarily diagnosed a newborn baby, who had Tetralogy of Fallot, thumb agenesis, facial dysplasia, and right ear canal malformation, as HOS. Chromosome microarray analyses showed no pathological deletions or replications of chromosome segments; whole exome sequencing screened out six candidate genes that were involved in cardiac diseases or syndromes among which <italic>SALL4</italic> has been reported as HOS related gene. We evaluated the pathogenicity of <italic>SALL4</italic> mutant sites by series of software. The results indicated that SALL4-M143V may be a polymorphism site, and SALL4-R418C could cause disease. HOPE and SWISS PDB viewer showed that SALL4-R418C leads to changes in amino acid properties, loss of protein hydrogen bond, and functional impact of SALL4 zinc finger domain. These results further confirmed the pathogenic significance of SALL4-R418C mutant. When genetic analyses coupled with bioinformatic analyses, we identified a <italic>SALL4</italic> gene rare mutation which might contribute to a newborn with HOS. Although some doubts need to be further discussed and explored, our study deepened the understanding of phenotype difference among syndromes and role of <italic>SALL4</italic> mutations in disease occurrence.
- Subjects
HOLT-Oram syndrome; CONGENITAL heart disease; EAR canal; HEART diseases; GENETIC polymorphisms; AMINO acids
- Publication
DNA & Cell Biology, 2018, Vol 37, Issue 4, p398
- ISSN
1044-5498
- Publication type
Article
- DOI
10.1089/dna.2017.4094