AMPK Methods and Protocols

variably styledPRKAG2cardiac syndrome,PRKAG2cardiomyop-

athy, orPRKAG2disease—these seminal reports fuelled intense

scientific interest into the cardiac functions of AMPK [14–16].

2 Clinical Genetics ofPRKAG2Mutations

Multiple distinct heterozygous variants inPRKAG2have been

described in association with a highly penetrant cardiac phenotype

(Table1), most frequently Arg302Gln and Asn488Ile which con-

stitute ~57% and ~21% of cases, respectively [17]. The great major-

ity of these variants are missense substitutions located in the

adenine nucleotide binding CBS domains [18]. Moreover, the

Arg302Gln mutation is homologous in location to a naturally

occurring dominant mutation (Arg200Gln) in CBS1 ofγ3in

Fig. 1Pedigree of a family with PRKAG2 cardiomyopathy and causal missense

mutation. Upper panel, pedigree of a family with aPRKAG2mutation (in this case

Arg531Gly) illustrating autosomal dominant transmission. Affected members are

denoted by solid symbols, square symbols indicate males, and circles indicate

females. Crossed through symbols denote individuals who suffered premature

sudden cardiac death. Lower panel, identification of the causal PRKAG2

mutation by DNA sequencing (Reproduced from ref.30 with permission from

Wolters Kluwer Health, Inc.)

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