Jervell and Lange-Nielsen syndrome: Difference between revisions
Jump to navigation
Jump to search
| Line 73: | Line 73: | ||
* ''[[KCNQ1|KCNE1]]'' [[gene]] normally consists of 3 [[Exon|exons]] and have a general spanning of 40 kb.<ref name="pmid14679187">{{cite journal| author=Lewis A, McCrossan ZA, Abbott GW| title=MinK, MiRP1, and MiRP2 diversify Kv3.1 and Kv3.2 potassium channel gating. | journal=J Biol Chem | year= 2004 | volume= 279 | issue= 9 | pages= 7884-92 | pmid=14679187 | doi=10.1074/jbc.M310501200 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14679187 }}</ref><ref name="pmid12923204">{{cite journal| author=Lu Y, Mahaut-Smith MP, Huang CL, Vandenberg JI| title=Mutant MiRP1 subunits modulate HERG K+ channel gating: a mechanism for pro-arrhythmia in long QT syndrome type 6. | journal=J Physiol | year= 2003 | volume= 551 | issue= Pt 1 | pages= 253-62 | pmid=12923204 | doi=10.1113/jphysiol.2003.046045 | pmc=2343156 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12923204 }}</ref><ref name="pmid16050264">{{cite journal| author=Anantharam A, Abbott GW| title=Does hERG coassemble with a beta subunit? Evidence for roles of MinK and MiRP1. | journal=Novartis Found Symp | year= 2005 | volume= 266 | issue= | pages= 100-12; discussion 112-7, 155-8 | pmid=16050264 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16050264 }}</ref><ref name="pmid118749882">{{cite journal| author=Abbott GW, Goldstein SA| title=Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism. | journal=FASEB J | year= 2002 | volume= 16 | issue= 3 | pages= 390-400 | pmid=11874988 | doi=10.1096/fj.01-0520hyp | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11874988 }}</ref><ref name="pmid179933272">{{cite journal| author=Abbott GW, Xu X, Roepke TK| title=Impact of ancillary subunits on ventricular repolarization. | journal=J Electrocardiol | year= 2007 | volume= 40 | issue= 6 Suppl | pages= S42-6 | pmid=17993327 | doi=10.1016/j.jelectrocard.2007.05.021 | pmc=2128763 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17993327 }}</ref> | * ''[[KCNQ1|KCNE1]]'' [[gene]] normally consists of 3 [[Exon|exons]] and have a general spanning of 40 kb.<ref name="pmid14679187">{{cite journal| author=Lewis A, McCrossan ZA, Abbott GW| title=MinK, MiRP1, and MiRP2 diversify Kv3.1 and Kv3.2 potassium channel gating. | journal=J Biol Chem | year= 2004 | volume= 279 | issue= 9 | pages= 7884-92 | pmid=14679187 | doi=10.1074/jbc.M310501200 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14679187 }}</ref><ref name="pmid12923204">{{cite journal| author=Lu Y, Mahaut-Smith MP, Huang CL, Vandenberg JI| title=Mutant MiRP1 subunits modulate HERG K+ channel gating: a mechanism for pro-arrhythmia in long QT syndrome type 6. | journal=J Physiol | year= 2003 | volume= 551 | issue= Pt 1 | pages= 253-62 | pmid=12923204 | doi=10.1113/jphysiol.2003.046045 | pmc=2343156 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12923204 }}</ref><ref name="pmid16050264">{{cite journal| author=Anantharam A, Abbott GW| title=Does hERG coassemble with a beta subunit? Evidence for roles of MinK and MiRP1. | journal=Novartis Found Symp | year= 2005 | volume= 266 | issue= | pages= 100-12; discussion 112-7, 155-8 | pmid=16050264 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16050264 }}</ref><ref name="pmid118749882">{{cite journal| author=Abbott GW, Goldstein SA| title=Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism. | journal=FASEB J | year= 2002 | volume= 16 | issue= 3 | pages= 390-400 | pmid=11874988 | doi=10.1096/fj.01-0520hyp | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11874988 }}</ref><ref name="pmid179933272">{{cite journal| author=Abbott GW, Xu X, Roepke TK| title=Impact of ancillary subunits on ventricular repolarization. | journal=J Electrocardiol | year= 2007 | volume= 40 | issue= 6 Suppl | pages= S42-6 | pmid=17993327 | doi=10.1016/j.jelectrocard.2007.05.021 | pmc=2128763 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17993327 }}</ref> | ||
* The normal [[gene]] product of ''[[KvLQT1|KCNE1]]'' gene is potassium voltage-gated channel subfamily E member 1. | * The normal [[gene]] product of ''[[KvLQT1|KCNE1]]'' gene is [[potassium]] [[Voltage-gated ion channel|voltage-gated]] channel subfamily E member 1. | ||
* Potassium voltage-gated channel subfamily E member 1 is also called as minK potassium channel protein beta subunit.<ref name="pmid19219384">{{cite journal| author=McCrossan ZA, Roepke TK, Lewis A, Panaghie G, Abbott GW| title=Regulation of the Kv2.1 potassium channel by MinK and MiRP1. | journal=J Membr Biol | year= 2009 | volume= 228 | issue= 1 | pages= 1-14 | pmid=19219384 | doi=10.1007/s00232-009-9154-8 | pmc=2849987 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19219384 }}</ref> | *[[Potassium]] [[Voltage-gated ion channel|voltage-gated]] channel subfamily E member 1 is also called as minK potassium channel protein beta subunit.<ref name="pmid19219384">{{cite journal| author=McCrossan ZA, Roepke TK, Lewis A, Panaghie G, Abbott GW| title=Regulation of the Kv2.1 potassium channel by MinK and MiRP1. | journal=J Membr Biol | year= 2009 | volume= 228 | issue= 1 | pages= 1-14 | pmid=19219384 | doi=10.1007/s00232-009-9154-8 | pmc=2849987 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19219384 }}</ref> | ||
* When ''[[KCNQ1|KCNE1]]'' gene undergoes missense mutation it results in yielding truncated protein. | * When ''[[KCNQ1|KCNE1]]'' gene undergoes [[Missense mutation|missense]] [[mutation]] it results in yielding truncated [[protein]]. | ||
* Then the truncated protein results in impairing potassium channel function, which is known to result in long QT syndrome. | * Then the truncated protein results in impairing [[potassium channel]] function, which is known to result in [[long QT syndrome]]. | ||
== Genetics == | == Genetics == | ||
Revision as of 14:07, 15 November 2019
| Jervell and Lange-Nielsen syndrome | |
| ICD-9 | 426.82 |
|---|---|
| OMIM | 220400 |
| DiseasesDB | 7249 |
| MeSH | D029593 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Synonyms and keywords:Autosomal recessive long QT syndrome (LQTS), cardioauditory syndrome, cardioauditory syndrome of Jervell and Lange-Nielsen, deafness, congenital, and functional heart disease, Jervell and Lange-Nielsen (JLNS), surdocardiac syndrome
Overview
Jervell and Lange-Nielsen syndrome is a rare autosomal recessive condition that leads to sensorineural deafness, long QT syndrome (LQTS) and other cardiac events. Jervell and Lange-Nielsen syndrome is due to KCNQ1 or KCNE1 gene mutations. The range of symptoms and severity of symptoms in Jervell and Lange-Nielsen syndrome differs from patient to patient.
Historical Perspective
- Jervell and Lange-Nielsen syndrome (JLNS) was first discovered by Anton Jervell a Norwegian physician and Fred Lange-Nielsen a Norwegian doctor and jazz musician, in 1957.[1]
Classification
| Type | Chromosome Locus | Gene Mutation | Protein Involved |
| Jervell and Lange-Nielsen syndrome 1 | 11p15.5-p15.4 | KCNQ1 | Potassium voltage-gated channel subfamily KQT member 1 |
| Jervell and Lange-Nielsen syndrome 2 | 21q22.12 | KCNE1 | Potassium voltage-gated channel subfamily E member 1 |
Pathophysiology
Physiology
The normal physiology of KCNQ1 and KCNE1 genes can be understood as follows:[5]
- Both KCNQ1 and KCNE1 genes encodes for the slow potassium channel currents of the cochlea and the heart.
- Normally the the slow potassium channel currents were stimulated by the sound, when stimulated the potassium from the scala media passes the action potential through the apex of the hair cells.
- The potassium action potential then depolarise the hair cells.
- Once depolarised there is a release calcium-channel-induced release of neurotransmitter.
- The neurotransmitter then passes along with the auditory nerve and then depolarize and the currents are sent centrally where they are received as sound.
Pathogenesis
- It is understood that Jervell and Lange-Nielsen syndrome (JLNS) is the result of mutations in the gene KCNQ1 and KCNE1.[6]
- KCNQ1 gene normally consists of 16 exons and have a general spanning of 400 kb.[7][8][9]
- The normal gene product of KCNQ1 gene is potassium voltage-gated channel subfamily KQT member 1.
- When KCNQ1 gene undergoes frameshift mutation it results in yielding truncated protein.
- Then the truncated protein either delete or duplicate the exons of the KCNQ1 gene and results in abnormal gene product which is known to result in long QT syndrome.
- KCNE1 gene normally consists of 3 exons and have a general spanning of 40 kb.[10][11][12][13][14]
- The normal gene product of KCNE1 gene is potassium voltage-gated channel subfamily E member 1.
- Potassium voltage-gated channel subfamily E member 1 is also called as minK potassium channel protein beta subunit.[15]
- When KCNE1 gene undergoes missense mutation it results in yielding truncated protein.
- Then the truncated protein results in impairing potassium channel function, which is known to result in long QT syndrome.
Genetics
- Jervell and Lange-Nielsen syndrome (JLNS) is transmitted in autosomal recessive pattern.
- Genes involved in the pathogenesis of Jervell and Lange-Nielsen syndrome (JLNS) include:
Causes
Genetic Causes
- [Disease name] is caused by a mutation in the [gene name] gene.
Differentiating Xyz from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Treatment
References
- ↑ Tranebjaerg L, Bathen J, Tyson J, Bitner-Glindzicz M (1999). "Jervell and Lange-Nielsen syndrome: a Norwegian perspective". Am J Med Genet. 89 (3): 137–46. PMID 10704188.
- ↑ Tyson J, Tranebjaerg L, McEntagart M, Larsen LA, Christiansen M, Whiteford ML; et al. (2000). "Mutational spectrum in the cardioauditory syndrome of Jervell and Lange-Nielsen". Hum Genet. 107 (5): 499–503. doi:10.1007/s004390000402. PMID 11140949.
- ↑ Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K; et al. (2006). "The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome". Circulation. 113 (6): 783–90. doi:10.1161/CIRCULATIONAHA.105.592899. PMID 16461811.
- ↑ Tranebjaerg L, Bathen J, Tyson J, Bitner-Glindzicz M (1999). "Jervell and Lange-Nielsen syndrome: a Norwegian perspective". Am J Med Genet. 89 (3): 137–46. PMID 10704188.
- ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 20301579.
- ↑ Tranebjaerg L, Bathen J, Tyson J, Bitner-Glindzicz M (1999). "Jervell and Lange-Nielsen syndrome: a Norwegian perspective". Am J Med Genet. 89 (3): 137–46. PMID 10704188.
- ↑ Wang Z, Li H, Moss AJ, Robinson J, Zareba W, Knilans T; et al. (2002). "Compound heterozygous mutations in KvLQT1 cause Jervell and Lange-Nielsen syndrome". Mol Genet Metab. 75 (4): 308–16. doi:10.1016/S1096-7192(02)00007-0. PMID 12051962.
- ↑ Abbott GW, Xu X, Roepke TK (2007). "Impact of ancillary subunits on ventricular repolarization". J Electrocardiol. 40 (6 Suppl): S42–6. doi:10.1016/j.jelectrocard.2007.05.021. PMC 2128763. PMID 17993327.
- ↑ Abbott GW, Goldstein SA (2002). "Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism". FASEB J. 16 (3): 390–400. doi:10.1096/fj.01-0520hyp. PMID 11874988.
- ↑ Lewis A, McCrossan ZA, Abbott GW (2004). "MinK, MiRP1, and MiRP2 diversify Kv3.1 and Kv3.2 potassium channel gating". J Biol Chem. 279 (9): 7884–92. doi:10.1074/jbc.M310501200. PMID 14679187.
- ↑ Lu Y, Mahaut-Smith MP, Huang CL, Vandenberg JI (2003). "Mutant MiRP1 subunits modulate HERG K+ channel gating: a mechanism for pro-arrhythmia in long QT syndrome type 6". J Physiol. 551 (Pt 1): 253–62. doi:10.1113/jphysiol.2003.046045. PMC 2343156. PMID 12923204.
- ↑ Anantharam A, Abbott GW (2005). "Does hERG coassemble with a beta subunit? Evidence for roles of MinK and MiRP1". Novartis Found Symp. 266: 100–12, discussion 112-7, 155–8. PMID 16050264.
- ↑ Abbott GW, Goldstein SA (2002). "Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism". FASEB J. 16 (3): 390–400. doi:10.1096/fj.01-0520hyp. PMID 11874988.
- ↑ Abbott GW, Xu X, Roepke TK (2007). "Impact of ancillary subunits on ventricular repolarization". J Electrocardiol. 40 (6 Suppl): S42–6. doi:10.1016/j.jelectrocard.2007.05.021. PMC 2128763. PMID 17993327.
- ↑ McCrossan ZA, Roepke TK, Lewis A, Panaghie G, Abbott GW (2009). "Regulation of the Kv2.1 potassium channel by MinK and MiRP1". J Membr Biol. 228 (1): 1–14. doi:10.1007/s00232-009-9154-8. PMC 2849987. PMID 19219384.