From Hong Kong to Spain and Korea, QIAGEN’s Human Gene Mutation Database (HGMD) is helping researchers make strides in their work. The papers highlighted below provide only a few of the many recent instances in which HGMD was identified in the scientific literature as a resource for mutations related to disease and the interpretation of clinical test results.
Integrating functional analysis in the next generation sequencing diagnostic pipeline of RASopathies
First author: Gordon K. C. Leung
The results of a recent study in Nature’s Scientific Reports focused on variants of unknown significance (VUSs), which pose challenges during clinical interpretation and genetic counseling. A team from the University of Hong Kong investigated the potential of a diagnostic pipeline combining NGS and the functional assessment of variants, for which they used HGMD. They aimed to diagnose RASopathies, which are heterogeneous conditions caused by germline mutations in RAS/MAPK signaling pathway genes. As a result of their findings – classifying two genetic variants as likely pathogenic mutations – the report argues that establishing functional analysis for genetic syndromes would aid in long-term decision-making and lend itself to comprehensive interpretation of new variants.
Primary osteoporosis in young adults: genetic basis and identification of novel variants in causal genes
First author: Corinne Collet
To determine the causal genes of idiopathic osteoporosis in adulthood, a French team used HGMD to search for known pathogenic mutations in a cohort of 123 young/middle-aged adults. Their report, published in the Journal of Bone and Mineral Research, found that the clinical phenotype of patients carrying causal gene variants was indistinguishable. They did determine, however, that molecular screening of young osteoporotic adults revealed several variants, which might prove useful to identify susceptibility genes for personalizing treatment; this is particularly important for treatment with anabolic drugs.
Functional analyses of a novel splice variant in the CHD7 gene, found by next generation sequencing, confirm its pathogenicity in a Spanish patient and diagnose him with CHARGE syndrome
First author: Olatz Villate
Frontiers in Genetics recently published a report completed by a Spanish team who researched the functional consequences of a novel splice mutation in the CHD7 gene, which is largely responsible for CHARGE syndrome (an acronym for Coloboma, Heart defects, Atresia of the choanae, Retardation of growth and development, Genital hypoplasia and Ear abnormalities). Many of the features and symptoms of CHARGE syndrome are common to those of other syndromes, making it difficult to diagnose. The team used HGMD to place the incidence of splice mutations at 12%, enriching their understanding of the genetic causes of CHARGE syndrome, which will in turn aid in improving diagnosis and genetic counseling efforts in the future.
Detection of familial hypercholesterolemia using next generation sequencing in two population-based cohorts
First author: Hee Nam Kim
Researchers from Korea looked at familial hypercholesterolaemia (FH), a common autosomal dominant disorder. They classified pathogenic mutations by comparing all non-synonymous variants to HGMD. Though the team confirmed 17 mutations in 23 of their subjects, they also discovered that those with high total cholesterol levels had a low prevalence of FH mutations, leading them to conclude that that NGS-based testing at population levels would not be cost-effective.
When reading the scientific literature, we love to read reports of how our solutions contribute to furthering science and medicine. If you have a story of your own that you’d be willing to share with us, please get in touch! For a trial of HGMD, just click here.