Posts Categorized: Part 06: DIAGNOSTIC APPROACHES



Whole Exome Sequencing in Inborn errors of metabolism

Posted by & filed under Exome sequencing, Part 06: DIAGNOSTIC APPROACHES.

Therapies are becoming increasingly avaible for inborn errors of metabolism making diagnosis of these disorders particularly improtant. The New England Journal of Medicine recently published a study on whole-exome sequencing in 41 patients resulting in a diagnosis in 28 of them (68%) and a targeted intervention in 18 of them (44%). The relatively high diagnostic yield found in this study may stem […]



Post-zygotic Point Mutations

Posted by & filed under Part 06: DIAGNOSTIC APPROACHES.

My general practice in counseling families with a  child who has a suspected “de novo” dominant disorder is to estimate an approximate 5% recurrence risk for their future children based on potential gonadal mosaicism in the parents. However, a recent paper by Acuna-Hidalgo et al (AJHG, Volume 97, Issue 1, p67–74, 2 July 2015) presented work in which they found […]



Progress in nanopore technology

Posted by & filed under Exome sequencing, In the news, Part 06: DIAGNOSTIC APPROACHES, Tools.

Feng et al. (2015) recently reviewed the progress in nanopore technology from the past as well as the latest advances. They describe the different types of nanopores and discuss recent and potential applications. Nanopore-based sequencers have the potential to quickly and reliably sequence the entire human genome “for less than $1000, and possibly for even […]



Genomics to accelerate diagnosis of IEM

Posted by & filed under Part 06: DIAGNOSTIC APPROACHES, Tools.

Stranneheim et al. demonstrated how Massively parallel DNA sequencing (MPS) can aid in the diagnosis and early intervention of patients with Inborn Errors of Metabolism (IEM). Their method focuses on analysing pulsed whole genome sequence data in real time, using automated analysis combined with data reduction and parallelization. The genes targeted are 474 disease genes […]



New genomic technologies, PGD/Prenatal Genetics and society

Posted by & filed under Exome sequencing, Part 03: GENERAL THEMES, Part 06: DIAGNOSTIC APPROACHES.

As in every other field of science, the experts in medical genetics should collaborate closely with policy and law-makers to guide the usage of the new technologies. This is particularly important at present time in the context of the advancement of genomic technologies. A recent article by Farra et al. (retrospective cohort study) published in […]



Exome sequencing redefining phenotypes

Posted by & filed under Exome sequencing, Part 06: DIAGNOSTIC APPROACHES, Part 28: NEUROGENETICS, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT.

One would intuitively expect that Whole-exome sequencing (WES) will help broaden the phenotypic spectrum of known syndromes since in the past only patients closely matching the described phenotype of a documented genetic syndrome would be tested for the respective diagnosis. Some recent examples illustrating the direction the field is moving include the publications of Dr. […]



Archived neonatal dried blood spot samples for accurate whole genome sequencing

Posted by & filed under Exome sequencing, Newborn screening, Part 06: DIAGNOSTIC APPROACHES.

Hollegaard et al. have demonstrated in the past that DNA extracted from a fraction (2 × 3.2 mm discs) of an archived Dried blood spot sample (DBSS) can be whole genome amplified (wgaDNA) and used for accurate array genotyping. In this study, they compared whole-blood DNA next-generation sequencing (NGS) results to results from DBSS and concluded that DBSS […]



Incidental Findings in Clinical Exome/Genome Sequencing

Posted by & filed under Exome sequencing, Part 06: DIAGNOSTIC APPROACHES.

During the Annual Clinical Genetics Meeting of the American College of Medical Genetics and Genomics (ACMG) in Phoenix, the “ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing” were released. This report includes recommendations for management of incidental findings and for a minimum list of conditions, genes, and variants to be […]



Diagnostic exome sequencing in intellectual disability.

Posted by & filed under Exome sequencing, Part 06: DIAGNOSTIC APPROACHES, Part 28: NEUROGENETICS, Tools.

de Ligt et al. evaluated patients with intellectual disability to exclude known causes and then sequenced the coding regions of more than 21,000 genes obtained from 100 patients with an IQ below 50 and their unaffected parents. The total diagnostic yield was 16%, mostly involving de novo mutations. The authors conclude that de novo mutations […]



A new approach to advance clinical genomics?

Posted by & filed under Exome sequencing, Part 02: PERSPECTIVES, Part 03: GENERAL THEMES, Part 06: DIAGNOSTIC APPROACHES, Tools.

It is now feasible to sequence an individual’s whole genome at a relatively low cost. However, for genome sequencing to be implemented clinically, a number of major challenges need to be overcome. I hereby discuss the challenges associated with integrating genomic technologies into clinical practice and describe a novel approach, namely, “Individualized Mutation-weighed On-line Phenotype […]