A Japanese Patient with Lipoprotein Lipase Deficiency Homozygous for the Gly188Glu Mutation Prevalent Worldwide

抄録

We studied the molecular basis of familial lipoprotein lipase (LPL) deficiency in a new Japanese kindred. The proband was a four-month-old infant with severe hyperchylomicronemia. In postheparin plasma, LPL activity was virtually absent, although LPL mass was detectable. Single strand conformational polymorphism (SSCP) analysis showed an abnormal band with exon 5 of the LPL gene that was amplified by PCR from the proband's genomic DNA. DNA sequence analysis of the amplified fragment demonstrated that the proband was homozygous for a G-to-A change at nucleotide position 818 resulting in the substitution of glutamic acid for glycine at codon 188. Although this is among the first Gly188Glu mutations identified in Japanese, the missense mutation has previously been reported as a prevalent cause of familial LPL deficiency worldwide and has been proposed to have a common origin. However, DNA haplotype analysis with either restriction fragment length polymorphism (RFLP) or microsatellite markers revealed that the DNA haplotype of the proband was not identical to the haplotype previously reported as common to the other patients with the Gly188Glu mutation. These results add the Gly188Glu mutation to the growing list of LPL gene mutations underlying familial LPL deficiency in Japanese and indicate that the origin of the Gly188Glu mutation is not necessarily common but would be multicentric at least in part.