ALG9 Mutation Carriers Develop Kidney and Liver Cysts

Journal of the American Society of Nephrology : JASN
Whitney BesseTooraj Mirshahi

Abstract

Mutations in PKD1 or PKD2 cause typical autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic kidney disease. Dominantly inherited polycystic kidney and liver diseases on the ADPKD spectrum are also caused by mutations in at least six other genes required for protein biogenesis in the endoplasmic reticulum, the loss of which results in defective production of the PKD1 gene product, the membrane protein polycystin-1 (PC1). We used whole-exome sequencing in a cohort of 122 patients with genetically unresolved clinical diagnosis of ADPKD or polycystic liver disease to identify a candidate gene, ALG9, and in vitro cell-based assays of PC1 protein maturation to functionally validate it. For further validation, we identified carriers of ALG9 loss-of-function mutations and noncarrier matched controls in a large exome-sequenced population-based cohort and evaluated the occurrence of polycystic phenotypes in both groups. Two patients in the clinically defined cohort had rare loss-of-function variants in ALG9, which encodes a protein required for addition of specific mannose molecules to the assembling N-glycan precursors in the endoplasmic reticulum lumen. In vitro assays showed that inactivation of Alg9 result...Continue Reading

References

Dec 25, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Qi QianVicente E Torres
Jan 17, 2003·American Journal of Human Genetics·Airong LiStefan Somlo
Feb 11, 2003·Nature Genetics·Joost P H DrenthJan B M J Jansen
Aug 13, 2003·Kidney International·Arlene B ChapmanUNKNOWN Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort
May 11, 2004·Nature Genetics·Sonia DavilaStefan Somlo
Jun 7, 2006·Nature Reviews. Genetics·Hudson H Freeze
Apr 17, 2007·Lancet·Vicente E TorresYves Pirson
Mar 6, 2009·Clinical Journal of the American Society of Nephrology : CJASN·Amar D BansalDavid S Goldfarb
Apr 3, 2009·Clinical Journal of the American Society of Nephrology : CJASN·José L NishiuraIta P Heilberg
Mar 9, 2012·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Andrew D RuleTerri J Vrtiska
Apr 14, 2012·European Urology·Charles D ScalesUNKNOWN Urologic Diseases in America Project
Nov 18, 2014·The New England Journal of Medicine·Vicente E TorresUNKNOWN HALT-PKD Trial Investigators
Feb 13, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·David J CareyDavid H Ledbetter
Jun 9, 2016·Genome Biology·William McLarenFiona Cunningham
Aug 9, 2016·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Anja Pfau, Felix Knauf
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Sep 27, 2016·American Journal of Human Genetics·Nilah M IoannidisWeiva Sieh
Dec 3, 2016·Nucleic Acids Research·UNKNOWN The UniProt Consortium
Apr 5, 2017·Journal of the American Society of Nephrology : JASN·Oscar Rubio CabezasDetlef Bockenhauer
Sep 2, 2017·The Journal of Clinical Investigation·Whitney BesseStefan Somlo
Sep 22, 2017·Molecular Genetics and Metabolism Reports·Kellie DavisWalla Al-Hertani
Oct 19, 2017·Journal of the American Society of Nephrology : JASN·Emilie Cornec-Le GallPeter C Harris
May 1, 2018·American Journal of Human Genetics·Emilie Cornec-Le GallPeter C Harris
May 5, 2018·American Journal of Human Genetics·Jeffrey StaplesJeffrey G Reid
Jul 26, 2018·Journal of the American Society of Nephrology : JASN·Adrian Y TanHanna Rennert

❮ Previous
Next ❯

Citations

Oct 12, 2019·Journal of the American Society of Nephrology : JASN·Richard N Sandford
May 14, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Ria SchönauerJan Halbritter
Aug 19, 2020·Nature Reviews. Nephrology·Emily E GroopmanAli G Gharavi
Jul 22, 2020·Clinical Journal of the American Society of Nephrology : CJASN·Matthew B LanktreeYork Pei
Jun 2, 2020·Seminars in Cell & Developmental Biology·Ming Ma
Dec 8, 2020·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Harold M Aukema
Jan 28, 2021·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Pieter SchellekensDjalila Mekahli
Feb 9, 2021·European Journal of Medical Genetics·Melissa M BoerrigterJoost P H Drenth
Feb 14, 2021·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Guillaume DorvalLaurence Heidet
Jan 18, 2021·European Journal of Human Genetics : EJHG·Katherine A BensonPeter Conlon
Mar 8, 2021·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Charlotte GimpelDjalila Mekahli
May 8, 2021·Biochemical Society Transactions·Miguel Barroso-GilJohn A Sayer
Jul 13, 2021·Frontiers in Genetics·Jonathan de FalloisJan Halbritter
Aug 7, 2021·Biochimica Et Biophysica Acta. General Subjects·Matthew P Wilson, Gert Matthijs
Aug 4, 2021·Journal of Medical Case Reports·Daichi AkuzawaTatsuo Tsukamoto
Jul 8, 2020·Kidney International·Vinh T HuynhEmilie Cornec-Le Gall

❮ Previous
Next ❯

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.

Related Papers

American Journal of Medical Genetics. Part a
Michael WeinsteinNicola Poplawski
Journal of Research in Medical Sciences : the Official Journal of Isfahan University of Medical Sciences
Fatemeh Bitarafan, Masoud Garshasbi
La Revue du praticien
Emilie Cornec-Le Gall
© 2021 Meta ULC. All rights reserved