Cystinuria associated with different SLC7A9 gene variants in the cat (2023)

Abstract

Cystinuria is a classical inborn error of metabolism characterized by a selective proximal renal tubular defect affecting cystine, ornithine, lysine, and arginine (COLA) reabsorption, which can lead to uroliths and urinary obstruction. In humans, dogs and mice, cystinuria is caused by variants in one of two genes, SLC3A1 and SLC7A9, which encode the rBAT and bo,+ AT subunits of the bo,+ basic amino acid transporter system, respectively. In this study, exons and flanking regions of the SLC3A1 and SLC7A9 genes were sequenced from genomic DNA of cats (Felis catus) with COLAuria and cystine calculi. Relative to the Felis catus-6.2 reference genome sequence, DNA sequences from these affected cats revealed 3 unique homozygous SLC7A9 missense variants: one in exon 5 (p.Asp236Asn) from a non-purpose-bred medium-haired cat, one in exon 7 (p.Val294Glu) in a Maine Coon and a Sphinx cat, and one in exon 10 (p.Thr392Met) from a non-purpose-bred long-haired cat. A genotyping assay subsequently identified another cystinuric domestic medium-haired cat that was homozygous for the variant originally identified in the purebred cats. These missense variants result in deleterious amino acid substitutions of highly conserved residues in the bo,+ AT protein. A limited population survey supported that the variants found were likely causative. The remaining 2 sequenced domestic short-haired cats had a heterozygous variant at a splice donor site in intron 10 and a homozygous single nucleotide variant at a branchpoint in intron 11 of SLC7A9, respectively. This study identifies the first SLC7A9 variants causing feline cystinuria and reveals that, as in humans and dogs, this disease is genetically heterogeneous in cats.

Original languageEnglish (US)
Article numbere0159247
JournalPloS one
Volume11
Issue number7
DOIs
StatePublished - Jul 2016

Bibliographical note

Funding Information:
This study was in part supported by a grant from the National Institutes of Health (https://www.nih.gov/) OD 010939 and a Postdoctoral Fellowship for Research Abroad from Japan Society for the Promotion of Science (http://www.jsps.go.jp/english/eab/) to KM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We appreciate the assistance of the clinicians managing these cystinuric cats, the staff at the Minnesota Urolith Center, St. Paul, MN, Ms. Shurnevia Strickland in the Metabolic Genetic Laboratory, Philadelphia, PA and Dr. Adrian Sewell at Biocontrol, Ingelsheim, Germany.

Publisher Copyright:
© 2016 Mizukami et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publisher link

Other files and links

Fingerprint

Dive into the research topics of 'Cystinuria associated with different SLC7A9 gene variants in the cat'. Together they form a unique fingerprint.

View full fingerprint

Cite this

  • APA
  • Standard
  • Harvard
  • Vancouver
  • Author
  • BIBTEX
  • RIS

Mizukami, K., Raj, K., Osborne, C. A., & Giger, U. (2016). Cystinuria associated with different SLC7A9 gene variants in the cat. PloS one, 11(7), [e0159247]. https://doi.org/10.1371/journal.pone.0159247

Cystinuria associated with different SLC7A9 gene variants in the cat. / Mizukami, Keijiro; Raj, Karthik; Osborne, Carl A et al.

In: PloS one, Vol. 11, No. 7, e0159247, 07.2016.

(Video) Guidelines for Diagnosis and Management of the Cobalamin-Related Disorders & Severe MTHFR

Research output: Contribution to journalArticlepeer-review

Mizukami, K, Raj, K, Osborne, CA & Giger, U 2016, 'Cystinuria associated with different SLC7A9 gene variants in the cat', PloS one, vol. 11, no. 7, e0159247. https://doi.org/10.1371/journal.pone.0159247

Mizukami K, Raj K, Osborne CA, Giger U. Cystinuria associated with different SLC7A9 gene variants in the cat. PloS one. 2016 Jul;11(7). e0159247. https://doi.org/10.1371/journal.pone.0159247

Mizukami, Keijiro ; Raj, Karthik ; Osborne, Carl A et al. / Cystinuria associated with different SLC7A9 gene variants in the cat. In: PloS one. 2016 ; Vol. 11, No. 7.

@article{3ad91843dc8c49df889c23378af3ee78,

title = "Cystinuria associated with different SLC7A9 gene variants in the cat",

abstract = "Cystinuria is a classical inborn error of metabolism characterized by a selective proximal renal tubular defect affecting cystine, ornithine, lysine, and arginine (COLA) reabsorption, which can lead to uroliths and urinary obstruction. In humans, dogs and mice, cystinuria is caused by variants in one of two genes, SLC3A1 and SLC7A9, which encode the rBAT and bo,+ AT subunits of the bo,+ basic amino acid transporter system, respectively. In this study, exons and flanking regions of the SLC3A1 and SLC7A9 genes were sequenced from genomic DNA of cats (Felis catus) with COLAuria and cystine calculi. Relative to the Felis catus-6.2 reference genome sequence, DNA sequences from these affected cats revealed 3 unique homozygous SLC7A9 missense variants: one in exon 5 (p.Asp236Asn) from a non-purpose-bred medium-haired cat, one in exon 7 (p.Val294Glu) in a Maine Coon and a Sphinx cat, and one in exon 10 (p.Thr392Met) from a non-purpose-bred long-haired cat. A genotyping assay subsequently identified another cystinuric domestic medium-haired cat that was homozygous for the variant originally identified in the purebred cats. These missense variants result in deleterious amino acid substitutions of highly conserved residues in the bo,+ AT protein. A limited population survey supported that the variants found were likely causative. The remaining 2 sequenced domestic short-haired cats had a heterozygous variant at a splice donor site in intron 10 and a homozygous single nucleotide variant at a branchpoint in intron 11 of SLC7A9, respectively. This study identifies the first SLC7A9 variants causing feline cystinuria and reveals that, as in humans and dogs, this disease is genetically heterogeneous in cats.",

author = "Keijiro Mizukami and Karthik Raj and Osborne, {Carl A} and Urs Giger",

note = "Funding Information: This study was in part supported by a grant from the National Institutes of Health (https://www.nih.gov/) OD 010939 and a Postdoctoral Fellowship for Research Abroad from Japan Society for the Promotion of Science (http://www.jsps.go.jp/english/eab/) to KM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We appreciate the assistance of the clinicians managing these cystinuric cats, the staff at the Minnesota Urolith Center, St. Paul, MN, Ms. Shurnevia Strickland in the Metabolic Genetic Laboratory, Philadelphia, PA and Dr. Adrian Sewell at Biocontrol, Ingelsheim, Germany. Publisher Copyright: {\textcopyright} 2016 Mizukami et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2016",

(Video) Genomics of Kidney Disease: Genetics of Kidney Stone Disease

month = jul,

doi = "10.1371/journal.pone.0159247",

language = "English (US)",

volume = "11",

journal = "PLoS One",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "7",

}

TY - JOUR

T1 - Cystinuria associated with different SLC7A9 gene variants in the cat

AU - Mizukami, Keijiro

AU - Raj, Karthik

AU - Osborne, Carl A

AU - Giger, Urs

N1 - Funding Information:This study was in part supported by a grant from the National Institutes of Health (https://www.nih.gov/) OD 010939 and a Postdoctoral Fellowship for Research Abroad from Japan Society for the Promotion of Science (http://www.jsps.go.jp/english/eab/) to KM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We appreciate the assistance of the clinicians managing these cystinuric cats, the staff at the Minnesota Urolith Center, St. Paul, MN, Ms. Shurnevia Strickland in the Metabolic Genetic Laboratory, Philadelphia, PA and Dr. Adrian Sewell at Biocontrol, Ingelsheim, Germany.Publisher Copyright:© 2016 Mizukami et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

(Video) USMLE Hi-yield Genes and Chromosomes

PY - 2016/7

Y1 - 2016/7

N2 - Cystinuria is a classical inborn error of metabolism characterized by a selective proximal renal tubular defect affecting cystine, ornithine, lysine, and arginine (COLA) reabsorption, which can lead to uroliths and urinary obstruction. In humans, dogs and mice, cystinuria is caused by variants in one of two genes, SLC3A1 and SLC7A9, which encode the rBAT and bo,+ AT subunits of the bo,+ basic amino acid transporter system, respectively. In this study, exons and flanking regions of the SLC3A1 and SLC7A9 genes were sequenced from genomic DNA of cats (Felis catus) with COLAuria and cystine calculi. Relative to the Felis catus-6.2 reference genome sequence, DNA sequences from these affected cats revealed 3 unique homozygous SLC7A9 missense variants: one in exon 5 (p.Asp236Asn) from a non-purpose-bred medium-haired cat, one in exon 7 (p.Val294Glu) in a Maine Coon and a Sphinx cat, and one in exon 10 (p.Thr392Met) from a non-purpose-bred long-haired cat. A genotyping assay subsequently identified another cystinuric domestic medium-haired cat that was homozygous for the variant originally identified in the purebred cats. These missense variants result in deleterious amino acid substitutions of highly conserved residues in the bo,+ AT protein. A limited population survey supported that the variants found were likely causative. The remaining 2 sequenced domestic short-haired cats had a heterozygous variant at a splice donor site in intron 10 and a homozygous single nucleotide variant at a branchpoint in intron 11 of SLC7A9, respectively. This study identifies the first SLC7A9 variants causing feline cystinuria and reveals that, as in humans and dogs, this disease is genetically heterogeneous in cats.

AB - Cystinuria is a classical inborn error of metabolism characterized by a selective proximal renal tubular defect affecting cystine, ornithine, lysine, and arginine (COLA) reabsorption, which can lead to uroliths and urinary obstruction. In humans, dogs and mice, cystinuria is caused by variants in one of two genes, SLC3A1 and SLC7A9, which encode the rBAT and bo,+ AT subunits of the bo,+ basic amino acid transporter system, respectively. In this study, exons and flanking regions of the SLC3A1 and SLC7A9 genes were sequenced from genomic DNA of cats (Felis catus) with COLAuria and cystine calculi. Relative to the Felis catus-6.2 reference genome sequence, DNA sequences from these affected cats revealed 3 unique homozygous SLC7A9 missense variants: one in exon 5 (p.Asp236Asn) from a non-purpose-bred medium-haired cat, one in exon 7 (p.Val294Glu) in a Maine Coon and a Sphinx cat, and one in exon 10 (p.Thr392Met) from a non-purpose-bred long-haired cat. A genotyping assay subsequently identified another cystinuric domestic medium-haired cat that was homozygous for the variant originally identified in the purebred cats. These missense variants result in deleterious amino acid substitutions of highly conserved residues in the bo,+ AT protein. A limited population survey supported that the variants found were likely causative. The remaining 2 sequenced domestic short-haired cats had a heterozygous variant at a splice donor site in intron 10 and a homozygous single nucleotide variant at a branchpoint in intron 11 of SLC7A9, respectively. This study identifies the first SLC7A9 variants causing feline cystinuria and reveals that, as in humans and dogs, this disease is genetically heterogeneous in cats.

UR - http://www.scopus.com/inward/record.url?scp=84978924670&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978924670&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0159247

DO - 10.1371/journal.pone.0159247

M3 - Article

C2 - 27404572

AN - SCOPUS:84978924670

VL - 11

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e0159247

ER -

(Video) Capturing semi-dominant inheritance in the ClinGen Gene Curation Interface

FAQs

What is the cystinuria gene? ›

Cystinuria is caused by changes (mutations) in the SLC3A1 and SLC7A9 genes. These mutations result in the abnormal transport of cystine in the kidney and this leads to the symptoms of cystinuria. Cystinuria is inherited in an autosomal recessive pattern.

What chromosome does cystinuria affect? ›

Genetic studies of DNA from families with cystinuria reveal a defective gene located on chromosome 2. The gene that codes for the cystine transporter, initially termed rBAT, is now known as SLC3A1 (SLC for solute carrier) in the international Genome Database. A second cystinuria gene on chromosome 19 is called SLC7A9.

How does cystinuria affect cell membranes? ›

Two genes (SLC7A9 and SLC3A1) that form an amino acid transporter are known to be responsible for the disease. Variants that cause the disease disrupt amino acid transport across the cell membrane, leading to the build-up of relatively insoluble cystine, resulting in formation of stones.

Is cystinuria inherited? ›

To have the symptoms of cystinuria, you must inherit the faulty gene from both parents. Your children will also inherit a copy of the faulty gene from you. Cystinuria is caused by too much cystine in the urine.

Is there a cure for cystinuria? ›

Most people with cystinuria have recurring stones. It is a lifelong condition that can be controlled, but not cured.

How do you test for cystinuria? ›

A test called a urinalysis will be performed to look for the presence of cystine crystals, the pH of the urine and any coexisting issues, such as a urinary tract infection. Cystine crystals form in acidic urine (which has a lower pH). Another urine test called urine nitroprusside can screen for cystinuria.

Is cystinuria a chronic kidney disease? ›

It has been observed that cystinuric patients develop chronic kidney disease (CKD) even more commonly than usual stone formers [16,17,18]. Hypertension has been shown to be associated with CKD in cystinuria patients [19].

Is cystinosis the same as cystinuria? ›

Cystinuria is a different disorder from cystinosis, which is characterized by intracellular cystine accumulation leading to the Fanconi syndrome and progressive kidney failure. (See "Cystinosis".)

Videos

1. Health, Wearables and Big Data
(Stanford Center for Clinical Research)
2. GHIF Newborn Sequencing Workshop - April 5
(GA4GH)
3. The Path to Preventive Genomics
(CenterforBrainHealth)
4. Talks from the GHIF Newborn Sequencing Forum 2022
(Genomes2People)
5. The Path to Preventive Genomics, Dr. Robert Green
(Genomes2People)
6. Keynote Address: Intro to AI (Michael Snyder)
(Icahn School of Medicine)
Top Articles
Latest Posts
Article information

Author: Amb. Frankie Simonis

Last Updated: 02/14/2023

Views: 5681

Rating: 4.6 / 5 (76 voted)

Reviews: 83% of readers found this page helpful

Author information

Name: Amb. Frankie Simonis

Birthday: 1998-02-19

Address: 64841 Delmar Isle, North Wiley, OR 74073

Phone: +17844167847676

Job: Forward IT Agent

Hobby: LARPing, Kitesurfing, Sewing, Digital arts, Sand art, Gardening, Dance

Introduction: My name is Amb. Frankie Simonis, I am a hilarious, enchanting, energetic, cooperative, innocent, cute, joyous person who loves writing and wants to share my knowledge and understanding with you.