What is the role of the LQT5, 6, 7, 8, 9 and 10 genes in the etiology of long QT syndrome (LQTS)?

Updated: Nov 29, 2017
  • Author: Ali A Sovari, MD, FACP, FACC; Chief Editor: Mikhael F El-Chami, MD  more...
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Answer

The LQT5 gene encodes for the IKs potassium channel. Similar to LQT1, LQT5 is involved in a decreased outward current of potassium and in QT prolongation.

LQT6 involves mutations in the gene MiRP1, or KCNE2, which encodes for the potassium channel beta subunit MinK-related protein 1 (MiRP1). KCNE2 encodes for the beta subunits of IKr potassium channels.

The LQT7 gene (KCNJ2) encodes for potassium channel 2 protein, which plays an important role in inward repolarizing current (IKi), especially in phase 3 of the action potential. In this subtype, QT prolongation is less prominent than in other types, and the QT interval is sometimes in the normal range. Because potassium channel 2 protein is expressed in cardiac and skeletal muscle, Andersen syndrome is associated with skeletal abnormalities, such as short stature and scoliosis.

Mutations in the LQT8 gene (CACNA1C) cause loss of L-type calcium current. So far, a limited number of cases of Timothy syndrome have been reported. They have been associated with abnormalities such as congenital heart disease, cognitive and behavioral problems, musculoskeletal diseases, and immune dysfunction.

The LQT9 gene encodes for caveolin 3, a caveolae plasma membrane component protein involved in scaffolding proteins. The voltage-gated sodium channel (NaV b3) is associated with this protein. Functional studies have demonstrated that CAV3 mutations are associated with persistent late sodium current, and they have been reported in cases of sudden infant death syndrome (SIDS). [13] LQT9 and LQT4 serve as examples of LQTS with nonchannel mutations.

A novel mutation in the LQT10 gene encoding the protein Nab4, a subunit of the voltage-gated sodium channel of the heart, Na1.5 (gene SCN5), results in a positive shift in the inactivation of the sodium current. To date, only a single mutation in one patient has been described. [14]


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