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 language | English (US) |
|---|---|
| Article number | e0159247 |
| Journal | PloS one |
| Volume | 11 |
| Issue number | 7 |
| DOIs | |
| State | Published - 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
Find It
Other files and links
- (Video) Cystinuria - Usmle step 1 Biochemstry webinar based lecture
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.
Research output: Contribution to journal › Article › peer-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",
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.
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 -
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".)