Abstract
Familial amyloid polyneuropathy (FAP) is an autosomal dominant disorder originally and most frequently described in Portugal. The usual constituent amyloid fibril protein is transthyretin (TTR) and the most frequent mutation in the TTR gene associated with FAP (including all Portuguese cases) is that at position 30 (met 30). Three different TTR haplotypes have been described in association with the met 30 mutation in European patients. We studied the haplotypes of 27 families (24 French, 2 British and 1 Greek) with FAP met 30 by analysing three polymorphisms in introns of the TTR gene. We also studied 6 families (2 British, 3 French and 1 Spanish) with FAP tyr 77. There were two main haplotypes in French patients with FAP met 30, one most commonly seen in the French families of Portuguese descent which was the same haplotype as previously described in Portuguese patients (haplotype I) and another haplotype (III) detected in most informative French families not of Portuguese origin. The age of onset of symptoms was consistently later in French than in Portuguese patients and in patients with haplotype III as the disease-associated haplotype rather than haplotype I. British and French patients with the tyr 77 mutation had different haplotypes. The most likely explanation of these findings is multiple founders of both mutations.
Similar content being viewed by others
References
Almeida M de R, Sasaki H, Sasaki Y, Salvi F, Ferlini A, Costa PP, Saraiva MJ (1993) Haplotype analysis of different FAP individuals with methionine 30 mutation in Europe. Arq Med 3: 189–192
Andersson R (1970) Hereditary amyloidosis with polyneuropathy. Acta Med Scand 188:85–94
Andrade C (1952) A peculiar form of peripheral neuropathy: familial atypical generalised amyloidosis with special involvement of the peripheral nerves. Brain 75:408–427
Araki S, Kurihara T, Tawara S, Kuribayashi T (1980) Familial amyloidotic polyneuropathy in Japan. In: Glenner G, Costa PP, Freitas AF (eds) Amyloid and amyloidosis. Excerpta Medica, Amsterdam, pp 67–77
Benson MD II, Turpin JC, Lucotte G, Zeldenrust S, Benson MD (1993) A transthyretin variant (alanine 71) associated with familial amyloidotic polyneuropathy in a French family. J Med Genet 30:120–122
Bhatia K, Reilly M, Adams D, Davis MB, Hawkes CH, Thomas PK, Said G, Harding AE (1993) Transthyretin gene mutations in British and French patients with amyloid neuropathy. J Neurol Neurosurg Psychiatry 56:694–697
Costa P, Figueira AS, Bravo RR (1978) Amyloid fibril protein related to pre-albumin in familial amyloidotic polyneuropathy. Proc Natl Acad Sci 75: 4499–4503
Drugge U, Andersson R, Chizari F, Danielsson M, Holmgren G, Sandgren O, Sousa A (1993) Familial amyloidotic polyneuropathy in Sweden: a pedigree analysis. J Med Genet 30: 388–392
Genebank accession number M11518. Human serum prealbumin gene
Holt IJ, Harding AE, Middleton L, Chrysostomou G, Said G, King RHM, Thomas PK (1989) Molecular genetics of amyloid neuropathy in Europe. Lancet I: 524–526
Ii S, Sommer SS (1993) The high frequency of TTR Met30 in familial amyloidotic polyneuropathy is not due to a founder effect. Hum Mol Genet 2: 1303–1305
Ii S, Minnerath S, Ii K, Dyck PJ, Sommer SS (1991) Two-tiered DNA-based diagnosis of transthyretin amyloidosis reveals two novel point mutations. Neurology 41:893–898
Kito S, Itoga E, Kamiya K, Kishida T, Yamamura Y (1980) Studies on familial amyloid polyneuropathy in Ogawa village, Japan. Eur Neurol 19:141
Reilly MM, King RHM (1993) Familial amyloid polyneuropathy. Brain Pathol 3:165–176
Satier F, Nichols WC, Benson MD (1990) Diagnosis of familial amyloidotic polyneuropathy in France. Clin Genet 38:469–473
Wallace MR, Dwulet FE, Williams EC, Conneally PM, Benson MD (1988) Identification of a new hereditary amyloidosis prealbumin variant, Tyr-77, and detection of the gene by DNA analysis. J Clin Invest 81: 189–193
Yoshioka K, Furuya H, Sasaki H, Saraiva MJM, Costa PP, Sakaki Y (1989) Haplotype analysis of familial amyloidotic polyneuropathy. Hum Genet 82:9–13
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Reilly, M.M., Adams, D., Davis, M.B. et al. Haplotype analysis of French, British and other European patients with familial amyloid polyneuropathy (met 30 and tyr 77). J Neurol 242, 664–668 (1995). https://doi.org/10.1007/BF00866917
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00866917