MUTATION IN DHP RECEPTOR ALPHA-1 SUBUNIT (CACLN1A3) GENE IN A DUTCH FAMILY WITH HYPOKALEMIC PERIODIC PARALYSIS

Hypokalaemic periodic paralysis (HypoPP) is characterised by transient attacks of muscle weakness of varying duration and severity accompani ed by a drop in serum potassium concentration during the attacks. The largest known HypoPP family is of Dutch origin and consists of 277 mem bers in the last five generations, 55 of whom have HypoPP inherited in an autosomal dominant pattern. Forty-eight persons including 28 patie nts with a proven diagnosis of HypoPP were used for linkage analysis. Microsatellite markers were used to exclude 45 to 50% of the genome an d linkage to chromosome 1q31-32 was found. No recombinants were found between HypoPP and D1S412 and a microsatellite contained within the DH P receptor alpha 1 subunit (CACLN1A3) gene. A previously reported G to A mutation causing an arginine to histidine substitution at residue 5 28 in the transmembrane segment IIS4 of the CACLN1A3 gene was shown in patients by restriction analysis of genomic PCR products.