Genetics

It should be emphasized that all forms of WPW syndrome are likely due to genetic defects. Most cases with the WPW syndrome have an accessory pathway without conduction defects or hypertrophy. The form of WPW due to the PRKAG2 gene is inherited in an autosomal dominant pattern. The PRKAG2 gene located on chromosome 7q36 encodes the gamma 2 subunit of AMP-activated protein kinase (AMPK). AMP-activated protein kinase consists of three subunits, alpha, beta, and gamma, with each subunit encoded by a distinct gene.[5] The alpha subunit is the catalytic component, and the beta and gamma are regulatory units. The gamma subunit has the binding site for AMP which is essential for enzymatic activity. AMP-activated protein kinase is present in all tissues although there may be tissue specificity on the basis of isoforms present within the heterotrimeric enzyme. There are three isoforms of the beta and three isoforms of the gamma which are derived from alternate transcripts of the same gene. The genetic defect consists of mutations in the PRKAG2 gene which encodes for the gamma subunit. The initial mutation was a substitution of glutamine for arginine at residue 302. The PRKAG2 gene consists of 16 exons and is more than 280 kb. The AMPK subunit protein is 63 kDa.[6] Six mutations[ ] have been described as listed in Table 1, all of which are missense

Table 1 AMPK (PRKAG2) mutations responsible for WPW

Arg302Gly

Arg531Gly

Thr400Asn

Asn488Ile

His142Arg

Ins Leu mutation, except for the leucine insertion. Expression of two of these mutations, the R302Q[8] and N488 I,[9] as a transgenic in the mouse is associated with the WPW syndrome, cardiac hypertrophy, and abnormalities in the conduction system. The penetrance based on the few families so far studied is in the range of 70% to 80%.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

Get My Free Ebook


Post a comment