Jervell and Lange-Nielsen syndrome: Difference between revisions
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* ''[[KCNQ1]]'' [[gene]] normally consists of 16 [[Exon|exons]] and have a general spanning of 400 kb.<ref name="pmid12051962">{{cite journal| author=Wang Z, Li H, Moss AJ, Robinson J, Zareba W, Knilans T et al.| title=Compound heterozygous mutations in KvLQT1 cause Jervell and Lange-Nielsen syndrome. | journal=Mol Genet Metab | year= 2002 | volume= 75 | issue= 4 | pages= 308-16 | pmid=12051962 | doi=10.1016/S1096-7192(02)00007-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12051962 }}</ref> | * ''[[KCNQ1]]'' [[gene]] normally consists of 16 [[Exon|exons]] and have a general spanning of 400 kb.<ref name="pmid12051962">{{cite journal| author=Wang Z, Li H, Moss AJ, Robinson J, Zareba W, Knilans T et al.| title=Compound heterozygous mutations in KvLQT1 cause Jervell and Lange-Nielsen syndrome. | journal=Mol Genet Metab | year= 2002 | volume= 75 | issue= 4 | pages= 308-16 | pmid=12051962 | doi=10.1016/S1096-7192(02)00007-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12051962 }}</ref> | ||
*The normal [[gene]] product of ''[[KvLQT1|KCNQ1]]'' gene is [[potassium]] [[voltage-gated]] channel subfamily KQT member 1. | *The normal [[gene]] product of ''[[KvLQT1|KCNQ1]]'' gene is [[potassium]] [[voltage-gated]] channel subfamily KQT member 1. | ||
* When ''[[KCNQ1]]'' gene undergoes frameshift mutation it results in yielding | * 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.. | * 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]]''''' | |||
* ''[[KCNQ1|KCNE1]]'' [[gene]] normally consists of 3 [[Exon|exons]] and have a general spanning of 40 kb. | |||
* The normal [[gene]] product of ''[[KvLQT1|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. | |||
* When ''[[KCNQ1|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 == | == Genetics == | ||
Revision as of 15:11, 14 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 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
- KCNQ1 gene normally consists of 16 exons and have a general spanning of 400 kb.[6]
- 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.
- 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.
- 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:
OR
The development of [disease name] is the result of multiple genetic mutations such as:
- [Mutation 1]
- [Mutation 2]
- [Mutation 3]
Causes
Life-threatening Causes[edit | edit source]
- Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. There are no life-threatening causes of disease name, however complications resulting from untreated disease name is common.
- Life-threatening causes of [symptom/manifestation] include [cause1], [cause2], and [cause3].
- [Cause] is a life-threatening cause of [disease].
Common Causes[edit | edit source]
Common causes of [disease name] may include:
- [Cause1]
- [Cause2]
- [Cause3]
OR
- [Disease name] is caused by an infection with [pathogen name].
- [Pathogen name] is caused by [pathogen name].
Less Common Causes[edit | edit source]
Less common causes of [disease name] include:
- [Cause1]
- [Cause2]
- [Cause3]
Genetic Causes[edit | edit source]
- [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.
- ↑ 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.