Comparison between conventional and comprehensive sequencing approaches for genetic diagnosis of Alport syndrome

Molecular Genetics & Genomic Medicine
Tomohiko YamamuraKazumoto Iijima

Abstract

Alport syndrome (AS) is a hereditary disease caused by mutations in COL4A3-5 genes. Recently, comprehensive genetic analysis has become the first-line diagnostic tool for AS. However, no reports comparing mutation identification rates between conventional sequencing and comprehensive screening have been published. In this study, 441 patients clinically suspected of having AS were divided into two groups and compared. The initial mutational analysis method involved targeted exome sequencing using next-generation sequencing (NGS) (n = 147, NGS group) or Sanger sequencing for COL4A3/COL4A4/COL4A5 (n = 294, Sanger group). In the NGS group, 126 patients (86%) were diagnosed with AS by NGS, while two had pathogenic mutations in other genes, NPHS1 and EYA1. Further, 239 patients (81%) were diagnosed with AS by initial analysis in the Sanger group. Thirteen patients who were negative for mutation detection in the Sanger group were analyzed by NGS; three were diagnosed with AS. Two had mutations in CLCN5 or LAMB2. The final variant detection rate was 90%. Our results reveal that Sanger sequencing and targeted exome sequencing have high diagnostic ability. NGS also has the advantage of detecting other inherited kidney diseases and pathog...Continue Reading

References

Nov 1, 1996·Kidney International·C E Kashtan, A F Michael
Nov 16, 1999·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Y InoueN Yoshikawa
Jul 10, 2002·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Oliver GrossManfred Weber
Dec 18, 2007·Biochemical and Biophysical Research Communications·Takehiro KobayashiMakoto Uchiyama
Aug 30, 2008·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Stephen TonnaJudy Savige
Apr 10, 2010·Journal of the American Society of Nephrology : JASN·Mir Reza BekheirniaRobert W Schrier
Nov 13, 2010·Nephron. Clinical Practice·Clifford E Kashtan, Yoav Segal
Sep 8, 2011·European Journal of Human Genetics : EJHG·Rosangela ArtusoMirella Bruttini
Jan 26, 2013·Journal of the American Society of Nephrology : JASN·Judy SavigeFrances Flinter
Mar 19, 2014·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Masafumi OkaKazumoto Iijima
May 24, 2014·Journal of the American Society of Nephrology : JASN·Vincent MorinièreLaurence Heidet
Sep 4, 2014·Clinical Journal of the American Society of Nephrology : CJASN·Kandai NozuKazumoto Iijima
Jan 13, 2015·Journal of Medical Genetics·Maria Antonietta MencarelliAlessandra Renieri
Mar 6, 2015·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Rachel LennonAdrian S Woolf
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Jun 10, 2016·Clinical Journal of the American Society of Nephrology : CJASN·Naohiro KamiyoshiKazumoto Iijima
Dec 23, 2017·KI Reports·Tomohiko YamamuraKazumoto Iijima
Jul 1, 2018·Journal of the American Society of Nephrology : JASN·Tomoko HorinouchiKazumoto Iijima
Jul 11, 2018·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Judy SavigeHelen Storey

❮ Previous
Next ❯

Methods Mentioned

BETA
exome sequencing
reverse transcription PCR
PCR
electrophoresis
biopsy
XLAS
antisense nucleotides

Software Mentioned

NGS
Gene Mapper
SureCall

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.