Clinician-centric diagnosis of rare genetic diseases: performance of a gene pertinence metric in decision support for clinicians.

Orphanet Journal of Rare Diseases
Michael M SegalJoseph Gleeson

Abstract

In diagnosis of rare genetic diseases we face a decision as to the degree to which the sequencing lab offers one or more diagnoses based on clinical input provided by the clinician, or the clinician reaches a diagnosis based on the complete set of variants provided by the lab. We tested a software approach to assist the clinician in making the diagnosis based on clinical findings and an annotated genomic variant table, using cases already solved using less automated processes. For the 81 cases studied (involving 216 individuals), 70 had genetic abnormalities with phenotypes previously described in the literature, and 11 were not described in the literature at the time of analysis ("discovery genes"). These included cases beyond a trio, including ones with different variants in the same gene. In 100% of cases the abnormality was recognized. Of the 70, the abnormality was ranked #1 in 94% of cases, with an average rank 1.1 for all cases. Large CNVs could be analyzed in an integrated analysis, performed in 24 of the cases. The process is rapid enough to allow for periodic reanalysis of unsolved cases. A clinician-friendly environment for clinical correlation can be provided to clinicians who are best positioned to have the clinica...Continue Reading

References

Oct 13, 1983·The New England Journal of Medicine·J P Kassirer
May 27, 1982·The New England Journal of Medicine·D M Eddy, C H Clanton
Apr 12, 2013·Journal of Child Neurology·Michael M SegalSidney M Gospe
Nov 16, 2013·Nucleic Acids Research·Melissa J LandrumDonna R Maglott
Aug 27, 2014·Journal of Child Neurology·Michael M SegalJoseph Gleeson
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Apr 8, 2016·Applied & Translational Genomics·Michael M Segal
Jun 9, 2016·Genome Biology·William McLarenFiona Cunningham
Aug 18, 2016·Nature Genetics·Douglas M RuderferShaun M Purcell
Apr 25, 2019·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Joshua L DeignanUNKNOWN ACMG Laboratory Quality Assurance Committee

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Methods Mentioned

BETA
genotyping

Software Mentioned

XHMM
Genome
MarkDuplicates
bwa
Phen2Gene
GATK
ClinVar
PolyPhen
GERP
SimulConsult

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.