Abstract
The most frequent transthyretin (TTR) variant associated with hereditary amyloidosis is TTR Met 30, which has its major focus in Portugal, although it also occurs in many other countries. The distribution of the mutation and its occurrence in a CpG dinucleotide lead us to question the origin of the mutation and the possibility of its having originated in Portugal. In order to investigate these questions, we studied the distribution of haplotypes associated with the Met 30 mutation in families from different European countries. All the analysed Portuguese families presented the same haplotype associated with the Met 30 mutation (haplotype I). The same was found for the Swedish and Spanish families studied. However, a distinct haplotype (haplotype III) was found in three families, one Italian, one English and one Turkish. These results suggest that, although the Portuguese Met 30 carriers might have one founder, the mutation probably recurred in populations in Europe in a similar manner to that reported in Japan. In this study, we have also analysed the haplotypes associated with other TTR variants frequent in the Portuguese population.
This is a preview of subscription content, log in via an institution to check access.
References
Alves IL, Altland K, Almeida MR, Becher P, Costa PP, Saraiva MJM (1993) Screening of TTR variants in the Portuguese population by HIEF. J Rheumatol 20:185
Anderson R (1976) Familial amyloidosis with polyneuropathy. Acta Med Scand (Suppl) 590:1–64
Bastos Lima A, Martins da Silva A (1980) Clinical evaluation of late onset cases in type I (Andrade) amyloid neuropathy. In: Glenner GG, Costa PP, Freitas AF (eds) Amyloid and amyloidosis. Excerpta Medica, Amsterdam, pp 99–105
Cooper DM, Youssoufian H (1988) The CpG dinucleotide and human genetic disease. Hum Genet 78:151–155
Coutinho P, Martins da Silva A, Lopes Lima J, Resende Barbosa A (1980) Fourty years of experience with type I amyloid neuropathy (review of 483 cases). In: Glenner GG, Costa PP, Freitas AF (eds) Amyloid and amyloidosis. Excerpta Medica, Amsterdam, pp 88–98
Ferlini A, Romeo G, Tassinari CA, Saraiva MJM, Costa PP, Salvi F (1988) Discrimination of peripheral polyneuropathies caused by TTR variant or diabetes in the same pedigree through protein studies. Adv Neurol 48:201–208
Harrison HH, Gordon ED, Nichols WC, Benson MD (1991) Biochemical and clinical characterization of prealbumin Chicago: an apparently bening variant of serum prealbumin (transthyretin) discovered with high resolution two-dimensional electrophoresis. Am J Hum Genet 39:442–452
Holmgren G, Holmberg E, Lindstrom A, Nordenson I, Sandgren O, Steen L, Svensson B, Lundgren E, Gabain AV (1988) Diagnosis of familial amyloidotic polyneuropathy in Sweden by RFLP analysis. Clin Genet 33:176–180
Ii S, Sommer S (1993) The high frequency of TTR M30 in familial amyloidotic polyneuropathy is not due to a founder effect. Hum Mol Genet 2:1303–1305
Ii S, Sobell JL, Sommer S (1992) From molecular variant to disease: initial steps in evaluating the association of transthyretin M119 with disease. Am J Hum Genet 50:29–41
Jacobson DR, Reveille JD, Buxbaum JN (1991) Frequency and genetic background of the position 122 (Val-IIe) variant transthyretin gene in the Black population. Am J Hum Genet 49:192–198
Jacobson DR, Alves IL, Saraiva MJM, Thibodeau SN, Buxbaum JN (1995) Transthyretin Ser 6 gene frequency in individuals without amyloidosis. Hum Genet 95:308–312
Martinsn da Silva B, Santarem MM, Arala-Chaves MP (1980) Evidence for high incidence of HLA-A2 and HLA-A9 in patients afflicted with type I (Andrade) amyloid neuropathy-preliminary studies. In: Glenner GG, Costa PP, Freitas AF (eds) Amyloid and amyloidosis. Excerpta Medica, Amsterdam, pp 125–130
Munar-Qués M, Costa PP, Saraiva MJM (1990) The Majorcan focus of familial amyloidotic polyneuropathy type I. In: Costa PP, Falcão de Freitas A, Saraiva MJM (eds) Familial amyloidotic polyneuropathy and other transthyretin related disorders. Arq. Med. vol. 3, Porto, Portugal, pp 13–18
Nakazato M, Kangawa K, Minamino N, Tawara S, Matsuo H, Araki S (1984) Radioimmunoassay for detecting abnormal prealbumin in the serum for diagnosis of familial amyloidotic polyneuropathy (Japanese type). Biochem Biophys Res Commun 122:719–725
Salvi F, Ferlini A, Plasmati R, Rubboli G, Michelluci R, Forti A, Saraiva MJM (1990) Familial amyloidotic polyneuropathy in Italy. Arq Med 3:19–24
Saraiva MJM (1993) Transthyretin and familial amyloidotic polyneuropathy. In: Rosenberg RN, Prusiner SB, Di Mauro S, Barchi RL, Kunkel LM (eds) The molecular and genetic basis of neurological disease. Butterworths, Boston, pp 889–894
Saraiva MJM, Sherman W, Goodman DS (1986) Presence of a plasma transthyretin (prealbumin) variant in familial amyloidotic polyneuropathy in a kindred of Greek origin. J Lab Clin Med 108:17–22
Saraiva MJM, Costa PP, Goodman DS (1988) Transthyretin (prealbumin) in familial amyloidotic polyneuropathy: genetic and functional aspects. Adv Neurol 48:189–200
Saraiva MJM, Almeida MR, Alves IL, Moreira P, Gawinowicz MA, Costa PP, Rauh S, Banhzoff A, Altland K (1991) Molecular analyses of an acidic transthyretin Asn 90 variant. Am J Hum Genet 48:1004–1008
Skare J, Yazici H, Erken E, Dede H, Cohen A, Milunsky A, Skinner M (1990) Homozygosity for the Met 30 transthyretin gene in a Turkish kindred with familial amyloidotic polyneuropathy. Hum Genet 86:89–90
Tawara S, Nakazato M, Kangawa K, Matsuo H, Araki S (1983) Identification of amyloid prealbumin variant in familial amyloidotic polyneuropathy (Japanese type). Biochem Biophys Res Commun 116:880–888
Yoshioka K, Sasaki H, Yoshioka N, Furuya H, Harada T, Kito S, Sakaki Y (1986) Structure of the mutant prealbumin gene responsible for familial amyloidotic polyneuropathy. Mol Biol Med 3:319–328
Yoshioka K, Furuya H, Sasaki H, Saraiva MJM, Costa PP, Sakaki Y (1989) Haplotype analysis of familial amyloidotic polyneuropathy — evidence for multiple origins of the Val-Met mutation most common to the disease. Hum Genet 82:9–13
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Almeida, M.R., Aoyama-Oishi, N., Sakaki, Y. et al. Haplotype analysis of common transthyretin mutations. Hum Genet 96, 350–354 (1995). https://doi.org/10.1007/BF00210422
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00210422