Haplotype analysis of the transthyretin gene: Evidence for multiple recurrence of the Met30 mutation in the Caucasian population

Abstract

Familial amyloidotic polyneuropathy occurs most often as a result of mutations within the transthyretin (TTR) gene. Several of these mutations have been identified in multiple kindreds from different geographic and ethnic origins. In the present paper, we report a new haplotype analysis procedure based on polymerase chain reaction induced mutation restriction analysis (PCR-IMRA). This procedure, which is capable of distinguishing polymorphisms at six sites within the TTR gene, was used to compare the haplotypes of several independent Caucasian kindreds manifesting the Mct30, Ala60, and Ser84 TTR variants, as well as to demonstrate the utility of the new PCR-IMRA procedure for the study of TTR related hereditary amyloidosis. Our results suggest that the Met30 TTR variant has been caused by multiple mutational events in the Caucasian population. However, haplotypes were identical for Ser84 kindreds in the USA and Hungary, and for Ala60 kindreds in the USA and Australia, which may suggest common origins for the respective mutations within these kindreds.

Key Words:

• TRANSTHYRETIN (TTR)
• AMYLOIDOSIS
• POLYMERASE CHAIN REACTION(PCR)
• HAPLOTYPE
• RESTRICTION FRAGMENT LENGTH POLYMORPHISMS(RFLP)