Ml'tation analysis of carttltine palmitoyl transferase deficiency

Carnitine palmitoyl transferase (CPT2) deficiency is the most common lipid myopathy in humans. The adult onset phenotype is characterized by muscle pain,stiffness and myoglobinuria after exercise or fasting. CPT2 deficiency is usually detected by enzymatic analysis of skeletal muscle biopsies,however, the identification of CPT2 gene mutations makes it possible to perform mutation screening of blood or buccal cells.CPT2 deficiency is thought to be an autosomal recessive trait,although some first degree relatives of de fie lent pat ients exhibit clinical symptoms.The objectives of our study were:(1)to screen a group of individuals with reduced CPT2 activity(>2SD below the normal reference mean) for 10 mutât ions using alléle specific oligonucleotldes(ASO), (2)to identify new CPT2 mutations,(3)to determine the relative frequency of CPT2 mutations and(4)to correlate the mutation(s) identified with the CPT2 activity observed in the samples. 12 individuals were Identified with mutations(2 homozygotes,5 compound hétérozygotes and 5 hétérozygotes)The two most common mutât ions were Ser 113Leu(50% of mutant alleles) and Phe448Leu(17% of mutant alleles). Two new mutations were identified(Gly5A9Asp and Arg503Cys). A 2-nt deletion was found to be associated with a previously reported exon 4 mutation. ASO based assays were developed to rapidly screen for 13 CPT2 mutations that cause this lipid myopathy. Supported by the Muscular Dystrophy Association.