Polycystic kidney disease causes: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
m (Bot: Removing from Primary care) |
||
| (3 intermediate revisions by 2 users not shown) | |||
| Line 1: | Line 1: | ||
{{Polycystic kidney disease}} | {{Polycystic kidney disease}} | ||
{{CMG}} {{AE}} {{MKA}} [[User:Sergekorjian|Serge Korjian]], [[User:YazanDaaboul|Yazan Daaboul]] | {{CMG}}; {{AE}}{{MKA}}, [[User:Sergekorjian|Serge Korjian]], [[User:YazanDaaboul|Yazan Daaboul]] | ||
==Overview== | ==Overview== | ||
Polycystic kidney disease is a genetic disorder. Autosomal dominant polycystic kidney disease (ADPKD) is an autosomal dominant disorder due to the heterozygous inheritance of PKD1 (chromosome 16) or PKD2 (chromosome 4) gene mutations. Despite the disease being monogenic, phenotype is variable possibly due to a two-hit process, haploinsufficiency, or environmental factors. Autosomal recessive polycystic kidney disease (ARPKD) is caused by a mutation in the PKHD1 gene. | Polycystic kidney disease is a [[genetic]] disorder. [[Autosomal dominant polycystic kidney disease]] (ADPKD) is an [[autosomal dominant]] disorder due to the [[heterozygous]] [[inheritance]] of [[PKD1]] ([[chromosome 16]]) or [[PKD2]] ([[chromosome 4]]) [[gene]] mutations. Despite the disease being [[Monogenic disorder|monogenic]], [[phenotype]] is variable possibly due to a two-hit process, [[haploinsufficiency]], or environmental factors. [[Autosomal recessive polycystic kidney disease]] (ARPKD) is caused by a mutation in the [[PKHD1]] [[gene]]. | ||
==Causes== | ==Causes== | ||
===Genetic Causes=== | ===Genetic Causes=== | ||
*Autosomal dominant polycystic kidney disease (ADPKD) is caused by a mutation in either the PKD1 gene or PKD2 gene<ref name="pmid7736581">{{cite journal| author=| title=Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. The International Polycystic Kidney Disease Consortium. | journal=Cell | year= 1995 | volume= 81 | issue= 2 | pages= 289-98 | pmid=7736581 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7736581 }} </ref> | *[[Autosomal dominant polycystic kidney disease]] (ADPKD) is caused by a [[mutation]] in either the [[PKD1]] [[gene]] or [[PKD2]] [[gene]].<ref name="pmid7736581">{{cite journal| author=| title=Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. The International Polycystic Kidney Disease Consortium. | journal=Cell | year= 1995 | volume= 81 | issue= 2 | pages= 289-98 | pmid=7736581 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7736581 }} </ref> | ||
*ADPKD is an inherited disorder with 2 possible etiologic mutations | *ADPKD is an inherited disorder with 2 possible etiologic mutations. | ||
*'''PKD1''' mutations found on short arm of chromosome 16 (16p13.3) accounts for roughly 85% of cases<ref name="pmid8650545">{{cite journal| author=Mochizuki T, Wu G, Hayashi T, Xenophontos SL, Veldhuisen B, Saris JJ et al.| title=PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. | journal=Science | year= 1996 | volume= 272 | issue= 5266 | pages= 1339-42 | pmid=8650545 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8650545 }} </ref> | *'''PKD1''' mutations found on short arm of [[chromosome 16]] (16p13.3) accounts for roughly 85% of cases.<ref name="pmid8650545">{{cite journal| author=Mochizuki T, Wu G, Hayashi T, Xenophontos SL, Veldhuisen B, Saris JJ et al.| title=PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. | journal=Science | year= 1996 | volume= 272 | issue= 5266 | pages= 1339-42 | pmid=8650545 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8650545 }} </ref> | ||
*'''PKD2''' mutations found on the long arm of chromosome 4 (4q21) account for 15% of the remaining cases<ref name="pmid9611728">{{cite journal| author=Torra R, Badenas C, Darnell A, Nicolau C, Volpini V, Revert L et al.| title=[Clinical, genetic and molecular studies on autosomal dominant polycystic kidney disease]. | journal=Med Clin (Barc) | year= 1998 | volume= 110 | issue= 13 | pages= 481-7 | pmid=9611728 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9611728 }} </ref> | *'''PKD2''' mutations found on the long arm of [[chromosome 4]] (4q21) account for 15% of the remaining cases.<ref name="pmid9611728">{{cite journal| author=Torra R, Badenas C, Darnell A, Nicolau C, Volpini V, Revert L et al.| title=[Clinical, genetic and molecular studies on autosomal dominant polycystic kidney disease]. | journal=Med Clin (Barc) | year= 1998 | volume= 110 | issue= 13 | pages= 481-7 | pmid=9611728 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9611728 }} </ref> | ||
*All cases of ADPKD are heterozygous for either PKD mutations or both | *All cases of ADPKD are [[heterozygous]] for either PKD mutations or both. | ||
*Homozygous cases usually die in utero<ref name="pmid12087556">{{cite journal| author=Paterson AD, Wang KR, Lupea D, St George-Hyslop P, Pei Y| title=Recurrent fetal loss associated with bilineal inheritance of type 1 autosomal dominant polycystic kidney disease. | journal=Am J Kidney Dis | year= 2002 | volume= 40 | issue= 1 | pages= 16-20 | pmid=12087556 | doi=10.1053/ajkd.2002.33908 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12087556 }} </ref> | *[[Homozygous]] cases usually die in utero.<ref name="pmid12087556">{{cite journal| author=Paterson AD, Wang KR, Lupea D, St George-Hyslop P, Pei Y| title=Recurrent fetal loss associated with bilineal inheritance of type 1 autosomal dominant polycystic kidney disease. | journal=Am J Kidney Dis | year= 2002 | volume= 40 | issue= 1 | pages= 16-20 | pmid=12087556 | doi=10.1053/ajkd.2002.33908 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12087556 }} </ref> | ||
*Generally, PKD1 mutants have more severe renal disease with mean age at onset of ESRD around 50 years compared to 75 years in PKD2 mutants<ref name="pmid10023895">{{cite journal| author=Hateboer N, v Dijk MA, Bogdanova N, Coto E, Saggar-Malik AK, San Millan JL et al.| title=Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. | journal=Lancet | year= 1999 | volume= 353 | issue= 9147 | pages= 103-7 | pmid=10023895 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10023895 }} </ref> | *Generally, [[PKD1]] [[mutants]] have more severe renal disease with mean age at onset of [[ESRD]] around 50 years compared to 75 years in [[PKD2]] [[mutants]].<ref name="pmid10023895">{{cite journal| author=Hateboer N, v Dijk MA, Bogdanova N, Coto E, Saggar-Malik AK, San Millan JL et al.| title=Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. | journal=Lancet | year= 1999 | volume= 353 | issue= 9147 | pages= 103-7 | pmid=10023895 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10023895 }} </ref> | ||
*Patients heterozygous for both mutations have the most severe renal manifestations | *Patients [[heterozygous]] for both mutations have the most severe renal manifestations. | ||
*Despite the monogenic nature of the disease, the phenotype and severity of the disease as well as the extrarenal manifestations have been known to vary even within the same family | *Despite the [[Monogenic disorder|monogenic]] nature of the disease, the [[phenotype]] and severity of the disease as well as the extrarenal manifestations have been known to vary even within the same family. | ||
*Several mechanisms have been proposed to explain this variability including:<ref name="pmid17434405">{{cite journal| author=Torres VE, Harris PC, Pirson Y| title=Autosomal dominant polycystic kidney disease. | journal=Lancet | year= 2007 | volume= 369 | issue= 9569 | pages= 1287-301 | pmid=17434405 | doi=10.1016/S0140-6736(07)60601-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17434405 }} </ref> | *Several mechanisms have been proposed to explain this variability including:<ref name="pmid17434405">{{cite journal| author=Torres VE, Harris PC, Pirson Y| title=Autosomal dominant polycystic kidney disease. | journal=Lancet | year= 2007 | volume= 369 | issue= 9569 | pages= 1287-301 | pmid=17434405 | doi=10.1016/S0140-6736(07)60601-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17434405 }} </ref> | ||
**A two-hit hypothesis involving loss of two PKD alleles in both germline and somatic cell lines | **A two-hit hypothesis involving loss of two [[PKD]] [[alleles]] in both [[germline]] and [[somatic]] [[cell]] lines | ||
**Haploinsufficiency | **[[Haploinsufficiency]] | ||
**Environmental factors modifying disease processes | **Environmental factors modifying disease processes | ||
*Autosomal recessive polycystic kidney disease (ARPKD) is caused by a mutation in the PKHD1 gene<ref name="pmid11898128">{{cite journal |vauthors=Onuchic LF, Furu L, Nagasawa Y, Hou X, Eggermann T, Ren Z, Bergmann C, Senderek J, Esquivel E, Zeltner R, Rudnik-Schöneborn S, Mrug M, Sweeney W, Avner ED, Zerres K, Guay-Woodford LM, Somlo S, Germino GG |title=PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats |journal=Am. J. Hum. Genet. |volume=70 |issue=5 |pages=1305–17 |date=May 2002 |pmid=11898128 |pmc=447605 |doi=10.1086/340448 |url=}}</ref><ref name="pmid11919560">{{cite journal |vauthors=Ward CJ, Hogan MC, Rossetti S, Walker D, Sneddon T, Wang X, Kubly V, Cunningham JM, Bacallao R, Ishibashi M, Milliner DS, Torres VE, Harris PC |title=The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein |journal=Nat. Genet. |volume=30 |issue=3 |pages=259–69 |date=March 2002 |pmid=11919560 |doi=10.1038/ng833 |url=}}</ref> | *[[Autosomal recessive polycystic kidney disease]] (ARPKD) is caused by a [[mutation]] in the [[PKHD1]] [[gene]]<ref name="pmid11898128">{{cite journal |vauthors=Onuchic LF, Furu L, Nagasawa Y, Hou X, Eggermann T, Ren Z, Bergmann C, Senderek J, Esquivel E, Zeltner R, Rudnik-Schöneborn S, Mrug M, Sweeney W, Avner ED, Zerres K, Guay-Woodford LM, Somlo S, Germino GG |title=PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats |journal=Am. J. Hum. Genet. |volume=70 |issue=5 |pages=1305–17 |date=May 2002 |pmid=11898128 |pmc=447605 |doi=10.1086/340448 |url=}}</ref><ref name="pmid11919560">{{cite journal |vauthors=Ward CJ, Hogan MC, Rossetti S, Walker D, Sneddon T, Wang X, Kubly V, Cunningham JM, Bacallao R, Ishibashi M, Milliner DS, Torres VE, Harris PC |title=The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein |journal=Nat. Genet. |volume=30 |issue=3 |pages=259–69 |date=March 2002 |pmid=11919560 |doi=10.1038/ng833 |url=}}</ref> | ||
**PKHD1 is a gene that shares structural similarities with the hepatocyte growth-factor receptor | **[[PKHD1]] is a gene that shares structural similarities with the [[hepatocyte]] growth-factor [[receptor]]. | ||
==References== | ==References== | ||
| Line 29: | Line 29: | ||
[[Category:Up-To-Date]] | [[Category:Up-To-Date]] | ||
[[Category:Medicine]] | [[Category:Medicine]] | ||
[[Category:Nephrology]] | [[Category:Nephrology]] | ||
Latest revision as of 23:46, 29 July 2020
|
Polycystic kidney disease Microchapters |
|
Differentiating Polycystic kidney disease from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Polycystic kidney disease causes On the Web |
|
American Roentgen Ray Society Images of Polycystic kidney disease causes |
|
Risk calculators and risk factors for Polycystic kidney disease causes |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2], Serge Korjian, Yazan Daaboul
Overview
Polycystic kidney disease is a genetic disorder. Autosomal dominant polycystic kidney disease (ADPKD) is an autosomal dominant disorder due to the heterozygous inheritance of PKD1 (chromosome 16) or PKD2 (chromosome 4) gene mutations. Despite the disease being monogenic, phenotype is variable possibly due to a two-hit process, haploinsufficiency, or environmental factors. Autosomal recessive polycystic kidney disease (ARPKD) is caused by a mutation in the PKHD1 gene.
Causes
Genetic Causes
- Autosomal dominant polycystic kidney disease (ADPKD) is caused by a mutation in either the PKD1 gene or PKD2 gene.[1]
- ADPKD is an inherited disorder with 2 possible etiologic mutations.
- PKD1 mutations found on short arm of chromosome 16 (16p13.3) accounts for roughly 85% of cases.[2]
- PKD2 mutations found on the long arm of chromosome 4 (4q21) account for 15% of the remaining cases.[3]
- All cases of ADPKD are heterozygous for either PKD mutations or both.
- Homozygous cases usually die in utero.[4]
- Generally, PKD1 mutants have more severe renal disease with mean age at onset of ESRD around 50 years compared to 75 years in PKD2 mutants.[5]
- Patients heterozygous for both mutations have the most severe renal manifestations.
- Despite the monogenic nature of the disease, the phenotype and severity of the disease as well as the extrarenal manifestations have been known to vary even within the same family.
- Several mechanisms have been proposed to explain this variability including:[6]
- Autosomal recessive polycystic kidney disease (ARPKD) is caused by a mutation in the PKHD1 gene[7][8]
- PKHD1 is a gene that shares structural similarities with the hepatocyte growth-factor receptor.
References
- ↑ "Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. The International Polycystic Kidney Disease Consortium". Cell. 81 (2): 289–98. 1995. PMID 7736581.
- ↑ Mochizuki T, Wu G, Hayashi T, Xenophontos SL, Veldhuisen B, Saris JJ; et al. (1996). "PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein". Science. 272 (5266): 1339–42. PMID 8650545 Check
|pmid=value (help). - ↑ Torra R, Badenas C, Darnell A, Nicolau C, Volpini V, Revert L; et al. (1998). "[Clinical, genetic and molecular studies on autosomal dominant polycystic kidney disease]". Med Clin (Barc). 110 (13): 481–7. PMID 9611728.
- ↑ Paterson AD, Wang KR, Lupea D, St George-Hyslop P, Pei Y (2002). "Recurrent fetal loss associated with bilineal inheritance of type 1 autosomal dominant polycystic kidney disease". Am J Kidney Dis. 40 (1): 16–20. doi:10.1053/ajkd.2002.33908. PMID 12087556.
- ↑ Hateboer N, v Dijk MA, Bogdanova N, Coto E, Saggar-Malik AK, San Millan JL; et al. (1999). "Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group". Lancet. 353 (9147): 103–7. PMID 10023895.
- ↑ Torres VE, Harris PC, Pirson Y (2007). "Autosomal dominant polycystic kidney disease". Lancet. 369 (9569): 1287–301. doi:10.1016/S0140-6736(07)60601-1. PMID 17434405.
- ↑ Onuchic LF, Furu L, Nagasawa Y, Hou X, Eggermann T, Ren Z, Bergmann C, Senderek J, Esquivel E, Zeltner R, Rudnik-Schöneborn S, Mrug M, Sweeney W, Avner ED, Zerres K, Guay-Woodford LM, Somlo S, Germino GG (May 2002). "PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats". Am. J. Hum. Genet. 70 (5): 1305–17. doi:10.1086/340448. PMC 447605. PMID 11898128.
- ↑ Ward CJ, Hogan MC, Rossetti S, Walker D, Sneddon T, Wang X, Kubly V, Cunningham JM, Bacallao R, Ishibashi M, Milliner DS, Torres VE, Harris PC (March 2002). "The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein". Nat. Genet. 30 (3): 259–69. doi:10.1038/ng833. PMID 11919560.