Title: Samoyed hereditary glomerulopathy

[[File:Shuskey.jpg|thumb|right|Healthy Samoyed dog]]
'''Samoyed hereditary glomerulopathy''' ('''SHG''') is a hereditary, [[X-linked]], noninflammatory disease of the [[renal]] [[Glomerulus (kidney)|glomeruli]], occurring in the [[Samoyed (dog)|Samoyed]] breed of [[dog]]. The disease has been shown to be a model for [[Alport syndrome]] in humans&lt;ref name=Jansen&gt;{{cite journal |pmid=3651895 |year=1987 |last1=Jansen |first1=B |last2=Valli |first2=VE |last3=Thorner |first3=P |last4=Baumal |first4=R |last5=Lumsden |first5=JH |title=Samoyed hereditary glomerulopathy: serial, clinical and laboratory (urine, serum biochemistry and hematology) studies |volume=51 |issue=3 |pages=387–93 |pmc=1255344 |journal=Canadian Journal of Veterinary Research}}&lt;/ref&gt; in that the disease resembles that of the human disease. Because of this, it is sometimes referred to by the name given to the disease in humans when referring to the conditions in Samoyed dogs. Alternatively, it may also be known as X-linked hereditary nephritis. Genetically, the trait is inherited as a sex-linked, genetically dominant disease,&lt;ref&gt;{{cite journal|last=Jansen|first=B|author2=Tryphonas L |author3=Wong J |author4=Thorner P |author5=Maxie MG |author6=Valli VE |author7=Baumal R |author8=Basrur PK. |title=Mode of inheritance of Samoyed hereditary glomerulopathy: an animal model for hereditary nephritis in humans|journal=J Lab Clin Med|date=June 1986|volume=107|issue=6|series=(6)|pages=551–5|pmid=3711721}}&lt;/ref&gt; and thus affects male dogs to a greater degree than female dogs, since males only have one X chromosome.

==Description==
SHG is caused by a [[nonsense mutation]] in codon 1027 of the COL4A5 gene on the [[X chromosome]] ([[glycine]] to [[stop codon]]), which is similar to [[Alport syndrome]] in humans.&lt;ref&gt;{{cite journal |pmid=3711721 |year=1986 |last1=Jansen |first1=B |last2=Tryphonas |first2=L |last3=Wong |first3=J |last4=Thorner |first4=P |last5=Maxie |first5=MG |last6=Valli |first6=VE |last7=Baumal |first7=R |last8=Basrur |first8=PK |title=Mode of inheritance of Samoyed hereditary glomerulopathy: an animal model for hereditary nephritis in humans |volume=107 |issue=6 |pages=551–5 |journal=The Journal of Laboratory and Clinical Medicine}}&lt;/ref&gt; The disease is simply inherited, X-linked dominant, with males generally having more severe symptoms than females. Clinically, from the age of three to four months, [[proteinuria]] in both sexes is seen. In dogs older than this, [[kidney failure]] in combination with more or less pronounced hearing loss occurs swiftly, and death at the age of 8 to 15 months is expected. In [[heterozygous]] females, whereby only one of the two X chromosomes carry the mutation, the disease develops slowly.&lt;ref&gt;{{cite journal |pmid=8171024 |year=1994 |last1=Zheng |first1=K |last2=Thorner |first2=PS |last3=Marrano |first3=P |last4=Baumal |first4=R |last5=McInnes |first5=RR |title=Canine X chromosome-linked hereditary nephritis: a genetic model for human X-linked hereditary nephritis resulting from a single base mutation in the gene encoding the alpha 5 chain of collagen type IV |volume=91 |issue=9 |pages=3989–93 |pmc=43708 |journal=Proceedings of the National Academy of Sciences of the United States of America |doi=10.1073/pnas.91.9.3989|bibcode=1994PNAS...91.3989Z |doi-access=free }}&lt;/ref&gt;&lt;ref name=&quot;Chen&quot;/&gt;

The disease is specific to the Samoyed, in that the Samoyed is the only breed of dog to show the more rapid progression to kidney failure and death, as well as affecting males to a much more severe degree than females. The Samoyed, however, is not the only breed of dog to suffer from life-threatening renal diseases. Proteinuria has been found consistently in [[Samoyed (dog)|Samoyed]]s, [[Doberman Pinscher]]s, and [[Cocker spaniel]]s.&lt;ref name=Doberman&gt;{{cite journal |pmid=498006 |year=1979 |last1=Wilcock |first1=BP |last2=Patterson |first2=JM |title=Familial glomerulonephritis in Doberman pinscher dogs |volume=20 |issue=9 |pages=244–9 |pmc=1789598 |journal=The Canadian Veterinary Journal}}&lt;/ref&gt;&lt;ref name=Cocker&gt;{{cite journal |pages=15–24 |doi=10.1111/j.1748-5827.1984.tb00475.x |title=Familial nephropathy in the Cocker Spaniel |year=1984 |last1=Steward |first1=A. P. |last2=MacDougall |first2=D. F. |journal=Journal of Small Animal Practice |volume=25}}&lt;/ref&gt;

==Diagnosis==
Affected male and [[Hereditary carrier|carrier]] female dogs generally begin to show signs of the disease at two to three months of age, with proteinuria. By three to four months of age, symptoms include for affected male dogs: bodily wasting and loss of weight, proteinuria and [[hypoalbuminemia]]. Past nine months of age, [[hypercholesterolemia]] may be seen.&lt;ref name=&quot;Jansen&quot;/&gt; In the final stages of the disease, at around 15 months of age for affected males, symptoms are reported as being kidney failure, hearing loss and death. Since the condition is genetically dominant, diagnosis would also include analysis of the health of the sire and dam of the suspected affected progeny if available.

==Treatment==
The disease can be treated only to slow down the development, by use of [[cyclosporine A]]&lt;ref name=Chen&gt;{{cite journal |pages=690–8 |doi=10.1097/01.ASN.0000046964.15831.16 |title=Cyclosporine A Slows the Progressive Renal Disease of Alport Syndrome (X-Linked Hereditary Nephritis): Results from a Canine Model |year=2003 |last1=Chen |first1=D. |journal=Journal of the American Society of Nephrology |volume=14 |issue=3 |pmid=12595505 |last2=Jefferson |first2=B |last3=Harvey |first3=SJ |last4=Zheng |first4=K |last5=Gartley |first5=CJ |last6=Jacobs |first6=RM |last7=Thorner |first7=PS|doi-access=free }}&lt;/ref&gt;  and [[ACE inhibitor]]s, but not stopped or cured.&lt;ref name=Grodecki&gt;{{cite journal |pages=209–25 |doi=10.1016/S0021-9975(97)80016-3 |title=Treatment of X-linked hereditary nephritis in samoyed dogs with angiotensin converting enzyme (ACE) inhibitor |year=1997 |last1=Grodecki |first1=K |last2=Gains |first2=M |last3=Baumal |first3=R |last4=Osmond |first4=D |last5=Cotter |first5=B |last6=Valli |first6=V |last7=Jacobs |first7=R |journal=Journal of Comparative Pathology |volume=117 |issue=3 |pmid=9447482}}&lt;/ref&gt;

==References==
{{reflist|2}}

==Further reading==
* {{cite journal |pmid=3550289 |year=1987 |last1=Thorner |first1=P |last2=Jansen |first2=B |last3=Baumal |first3=R |last4=Valli |first4=VE |last5=Goldberger |first5=A |title=Samoyed hereditary glomerulopathy. Immunohistochemical staining of basement membranes of kidney for laminin, collagen type IV, fibronectin, and Goodpasture antigen, and correlation with electron microscopy of glomerular capillary basement membranes |volume=56 |issue=4 |pages=435–43 |journal=Laboratory Investigation}}
* {{cite journal |pmid=3799818 |year=1986 |last1=Jansen |first1=B |last2=Thorner |first2=P |last3=Baumal |first3=R |last4=Valli |first4=V |last5=Maxie |first5=MG |last6=Singh |first6=A |title=Samoyed hereditary glomerulopathy (SHG). Evolution of splitting of glomerular capillary basement membranes |volume=125 |issue=3 |pages=536–45 |pmc=1888463 |journal=The American Journal of Pathology}}
* {{cite journal |pmid=11380016 |year=2001 |last1=Rawdon |first1=TG |title=Juvenile nephropathy in a Samoyed bitch |volume=42 |issue=5 |pages=235–8 |journal=The Journal of Small Animal Practice |doi=10.1111/j.1748-5827.2001.tb02027.x}}
* {{cite journal |pages=2121–30 |doi=10.1111/j.1523-1755.2005.00668.x |title=Regulation of collagen type IV genes is organ-specific: Evidence from a canine model of Alport syndrome |year=2005 |last1=Zheng |first1=Keqin |last2=Perry |first2=Julie |last3=Harvey |first3=Scott J |last4=Sado |first4=Yoshikazu |last5=Ninomiya |first5=Yoshifumi |last6=Jefferson |first6=Barbara |last7=Jacobs |first7=Robert |last8=Hudson |first8=Billy G |last9=Thorner |first9=Paul S |journal=Kidney International |volume=68 |issue=5 |pmid=16221211 |doi-access=free }}

==External links==
* {{cite web |title=Hereditary Nephritis-Samoyed Hereditary Glomerulopathy |url=http://www.vetgen.com/canine-hereditary-nephritis.html |publisher=VetGen |accessdate=21 May 2011}}

[[Category:Genetic dog diseases]]
[[Category:Autoimmune diseases]]
[[Category:Glomerular diseases]]