Masaaki Nakamura

A novel variant of transthyretin (Glu89Lys) associated with familial amyloidotic polyneuropathy

We detected a point mutation in the transthyretin (TTR) gene associated with familial amyloidotic polyneuropathy (FAP) in a 57-year old male presenting with sensorimotor polyneuropathy, severe autonomic dysfunction and cardiomyopathy using a non-isotopic RNase cleavage assay (NIRCA). NIRCA suggested that the mutation site was near either amino acid position 58 of mature TTR or the 3′ end of exon 3. Direct DNA sequencing showed both a normal GA G (Glu) and a variantAAG (Lys) codon at amino acid position 89 of mature TTR, which has not been previously reported. The site of this mutation is near the 3′ end of exon 3, consistent with the result of NIRCA. This mutation was also confirmed by polymerase chain reaction-induced mutation restriction analysis (PCR-IMRA).

Cardiac amyloidosis associated with the transthyretin Ile122 mutation in a Caucasian family.

The Ile 122 transthyretin variant associated with restrictive cardiomyopathy has been described in African-Americans and estimated to be present in approximately 4% of the Black population. We report the first American-Caucasian family with cardiomyopathy due to the TTR lie122 mutation. The high prevalence of this mutation in the Black population and the discovery that it may cause disease in other ethnic populations highlights the importance of considering this autosomal dominant systemic amyloidosis in all individuals with restrictive cardiomyopathy. Inadequate diagnosis combined with inappropriate treatment may have a significant impact on morbidity and mortality.

Transthyretin isoleucine-122 mutation in African and American blacks

The gene frequency of the transthyretin (TTR) mutation (Vall22Ile) was studied in African and African-American populations. The African populations analyzed included the Zulu and Xhosa of South Africa, and Yorubas from the city of Ibadan, Nigeria. The African-American population included patients at the Veterans Affairs (VA) Medical Center, Indianapolis, and newborns from a local hospital in Indianapolis. The Vall22Ile TTR mutation was identified in I of 55 Zulu, 0 of 34 Xhosa, 0 of 9 Nigerian subjects, 5 of 51 Veteran patients, and 3 of 103 newborns. Assuming the 2.91% prevalence in newborns to be the norm, there is a significant increased prevalence in the VA patient population.

Identification of a New Transthyretin Variant (Ile49) in Familial Amyloidotic Polyneuropathy Using Electrospray Ionization Mass Spectrometry and Nonisotopic RNase Cleavage Assay

Mutation of the transthyretin (TTR) plasma protein and gene in a Japanese patient with amyloid polyneuropathy was investigated by electrospray ionization mass spectrometry (ESI-MS) and nonisotopic RNase cleavage assay (NIRCA), respectively. ESI-MS analysis showed normal TTR peaks and additionally a variant TTR with 12-dalton-higher molecular weight than normal TTR. NIRCA suggested that the mutation existed near either the 5′ or 3′ end of exon 3. Direct DNA sequencing revealed both a normal ACC (threonine) and a variant ATC (isoleucine) at codon 49, which was located near the 5′ end of exon 3. The molecular weight shift of this mutation was 12 D, consistent with the result of ESI-MS.