# 611818

LONG QT SYNDROME 9; LQT9


Other entities represented in this entry:

LONG QT SYNDROME 9, ACQUIRED, SUSCEPTIBILITY TO, INCLUDED
LONG QT SYNDROME 2/9, DIGENIC, INCLUDED; LQT2/9, DIGENIC, INCLUDED

Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
3p25.3 Long QT syndrome 9 611818 AD 3 CAV3 601253
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal dominant
CARDIOVASCULAR
Heart
- Prolongation of corrected QT interval
- Nonexertional syncope (in some patients)
- Sinus bradycardia (in some patients)
- Cardiac arrest (in some patients)
LABORATORY ABNORMALITIES
- Marked increase in late sodium current on voltage-clamp studies
MISCELLANEOUS
- Sudden unexplained infant death (SIDS) reported in some patients
MOLECULAR BASIS
- Caused by mutation in the caveolin 3 gene (CAV3, 601253.0016)

TEXT

A number sign (#) is used with this entry because long QT syndrome-9 (LQT9) is caused by heterozygous mutation in the CAV3 gene (601253), which encodes caveolin-3, on chromosome 3p25.

Digenic inheritance has also been reported; see MOLECULAR GENETICS.


Description

Congenital long QT syndrome is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncope, seizure, or sudden death (Jongbloed et al., 1999).

For a discussion of genetic heterogeneity of long QT syndrome, see LQT1 (192500).


Molecular Genetics

Vatta et al. (2006) analyzed the CAV3 gene (601253) in 905 unrelated patients with long QT syndrome who had previously been tested for mutations in known LQT genes; in 6 patients, they identified 4 heterozygous missense mutations (601253.0016-601253.0019, respectively) that were not found in more than 1,000 control alleles. Functional studies showed that the mutant caveolin-3 resulted in a 2- to 3-fold increase in the late sodium current of the cardiac sodium channel compared with wildtype.

Cronk et al. (2007) analyzed the CAV3 gene in necropsy tissue from 134 unrelated cases of sudden infant death syndrome (SIDS; 272120) and identified 3 missense mutations in 3 of 50 black infants (601253.0018; 601253.0020; 601253.0021). No mutations were detected in 1 Hispanic or 83 Caucasian infants. Voltage clamp studies demonstrated a gain-of-function phenotype for all 3 CAV3 mutations, with a 5-fold increase in late sodium current compared to controls.

Digenic Inheritance

Vatta et al. (2006) identified a long QT syndrome patient who had biallelic digenic mutations: a 14-year-old girl with nonexertional syncope and a 'seizure-like' presentation, who had U waves, sinus bradycardia, and a QTc of 405 ms on ECG, was found to carry a missense mutation in the LQT2-associated KCNH2 gene as well as a mutation in the CAV3 gene (see 601253.0018 and 152427.0024).


REFERENCES

  1. Cronk, L. B., Ye, B., Kaku, T., Tester, D. J., Vatta, M., Makielski, J. C., Ackerman, M. J. Novel mechanism for sudden infant death syndrome: persistent late sodium current secondary to mutations in caveolin-3. Heart Rhythm 4: 161-166, 2007. [PubMed: 17275750, images, related citations] [Full Text]

  2. Jongbloed, R. J. E., Wilde, A. A. M., Geelen, J. L. M. C., Doevendans, P., Schaap, C., Van Langen, I., van Tintelen, J. P., Cobben, J. M., Beaufort-Krol, G. C. M., Geraedts, J. P. M., Smeets, H. J. M. Novel KCNQ1 and HERG missense mutations in Dutch long-QT families. Hum. Mutat. 13: 301-310, 1999. [PubMed: 10220144, related citations] [Full Text]

  3. Vatta, M., Ackerman, M. J., Ye, B., Makielski, J. C., Ughanze, E. E., Taylor, E. W., Tester, D. J., Balijepalli, R. C., Foell, J. D., Li, Z., Kamp, T. J., Towbin, J. A. Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation 114: 2104-2112, 2006. [PubMed: 17060380, related citations] [Full Text]


Creation Date:
Marla J. F. O'Neill : 2/25/2008
joanna : 04/01/2022
carol : 04/23/2017
carol : 09/18/2015
alopez : 6/12/2014
alopez : 2/3/2012
carol : 1/14/2011
carol : 1/12/2011
carol : 3/18/2008
wwang : 2/26/2008

# 611818

LONG QT SYNDROME 9; LQT9


Other entities represented in this entry:

LONG QT SYNDROME 9, ACQUIRED, SUSCEPTIBILITY TO, INCLUDED
LONG QT SYNDROME 2/9, DIGENIC, INCLUDED; LQT2/9, DIGENIC, INCLUDED

ORPHA: 101016, 768;   DO: 0110650;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
3p25.3 Long QT syndrome 9 611818 Autosomal dominant 3 CAV3 601253

TEXT

A number sign (#) is used with this entry because long QT syndrome-9 (LQT9) is caused by heterozygous mutation in the CAV3 gene (601253), which encodes caveolin-3, on chromosome 3p25.

Digenic inheritance has also been reported; see MOLECULAR GENETICS.


Description

Congenital long QT syndrome is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncope, seizure, or sudden death (Jongbloed et al., 1999).

For a discussion of genetic heterogeneity of long QT syndrome, see LQT1 (192500).


Molecular Genetics

Vatta et al. (2006) analyzed the CAV3 gene (601253) in 905 unrelated patients with long QT syndrome who had previously been tested for mutations in known LQT genes; in 6 patients, they identified 4 heterozygous missense mutations (601253.0016-601253.0019, respectively) that were not found in more than 1,000 control alleles. Functional studies showed that the mutant caveolin-3 resulted in a 2- to 3-fold increase in the late sodium current of the cardiac sodium channel compared with wildtype.

Cronk et al. (2007) analyzed the CAV3 gene in necropsy tissue from 134 unrelated cases of sudden infant death syndrome (SIDS; 272120) and identified 3 missense mutations in 3 of 50 black infants (601253.0018; 601253.0020; 601253.0021). No mutations were detected in 1 Hispanic or 83 Caucasian infants. Voltage clamp studies demonstrated a gain-of-function phenotype for all 3 CAV3 mutations, with a 5-fold increase in late sodium current compared to controls.

Digenic Inheritance

Vatta et al. (2006) identified a long QT syndrome patient who had biallelic digenic mutations: a 14-year-old girl with nonexertional syncope and a 'seizure-like' presentation, who had U waves, sinus bradycardia, and a QTc of 405 ms on ECG, was found to carry a missense mutation in the LQT2-associated KCNH2 gene as well as a mutation in the CAV3 gene (see 601253.0018 and 152427.0024).


REFERENCES

  1. Cronk, L. B., Ye, B., Kaku, T., Tester, D. J., Vatta, M., Makielski, J. C., Ackerman, M. J. Novel mechanism for sudden infant death syndrome: persistent late sodium current secondary to mutations in caveolin-3. Heart Rhythm 4: 161-166, 2007. [PubMed: 17275750] [Full Text: https://doi.org/10.1016/j.hrthm.2006.11.030]

  2. Jongbloed, R. J. E., Wilde, A. A. M., Geelen, J. L. M. C., Doevendans, P., Schaap, C., Van Langen, I., van Tintelen, J. P., Cobben, J. M., Beaufort-Krol, G. C. M., Geraedts, J. P. M., Smeets, H. J. M. Novel KCNQ1 and HERG missense mutations in Dutch long-QT families. Hum. Mutat. 13: 301-310, 1999. [PubMed: 10220144] [Full Text: https://doi.org/10.1002/(SICI)1098-1004(1999)13:4<301::AID-HUMU7>3.0.CO;2-V]

  3. Vatta, M., Ackerman, M. J., Ye, B., Makielski, J. C., Ughanze, E. E., Taylor, E. W., Tester, D. J., Balijepalli, R. C., Foell, J. D., Li, Z., Kamp, T. J., Towbin, J. A. Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation 114: 2104-2112, 2006. [PubMed: 17060380] [Full Text: https://doi.org/10.1161/CIRCULATIONAHA.106.635268]


Creation Date:
Marla J. F. O'Neill : 2/25/2008

Edit History:
joanna : 04/01/2022
carol : 04/23/2017
carol : 09/18/2015
alopez : 6/12/2014
alopez : 2/3/2012
carol : 1/14/2011
carol : 1/12/2011
carol : 3/18/2008
wwang : 2/26/2008