{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T16:41:05Z","timestamp":1772815265496,"version":"3.50.1"},"reference-count":11,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1993,2]]},"abstract":"<jats:p>A transthyretin (TTR) mutation is described in a 44 year old French woman from Caen who presented at the age of 40 with neuropathy in all four extremities, diarrhoea, and orthostatic hypotension. Her father died with a similar syndrome including vitreous opacities. A nerve biopsy from the proband showed amyloid deposits which stained with anti-transthyretin. Direct genomic DNA sequencing of TTR exon 3 showed both thymine and cytosine in the position corresponding to the second base of codon 71. This codes for a variant alanine (GCG) as well as the normal valine (GTG), indicating that the proband is heterozygous for the substitution. Since this substitution does not result in the creation or abolition of a restriction endonuclease recognition site, a new technique (PCR-IMRA) was used to create an RFLP. Using a 24 bp nucleotide mutagenesis primer in the PCR reaction, a new NspBII site is created on amplification of the variant allele. With this method a 170 bp TTR exon 3 PCR product was generated for both the normal and the variant allele. On digestion of the PCR product with NspBII, DNA from a heterozygous subject showed both the 170 bp undigested product from the normal allele and a 146 bp digestion product from the variant allele. By PCR-IMRA, two of five children of the proband were positive for the variant allele. This non-radioactive technique gives a rapid method for testing subjects at risk for this mutation.<\/jats:p>","DOI":"10.1136\/jmg.30.2.120","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:23:16Z","timestamp":1226330596000},"page":"120-122","source":"Crossref","is-referenced-by-count":18,"title":["A transthyretin variant (alanine 71) associated with familial amyloidotic polyneuropathy in a French family."],"prefix":"10.1136","volume":"30","author":[{"suffix":"2nd","given":"M D","family":"Benson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J C","family":"Turpin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Lucotte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Zeldenrust","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"LeChevalier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M D","family":"Benson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1993,2,1]]},"reference":[{"key":"ref_1","first-page":"2439","article-title":"In: The metabolic basis of inherited disease","author":"Benson, M.D.; Amyloidosis, Wallace M.R.","year":"1989","unstructured":"Benson MD, Wallace MR. Amyloidosis. In: The metabolic basis of inherited disease, New York: McGraw-Hill, 1989:2439-60."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1172\/JCI114938","article-title":"A point mutation in transthyretin increases affinity for thyroxine and produces euthyroid hyperthyroxinemia","volume":"86","author":"Moses, A.C.; Rosen, H.N.; Moller, D.E.","year":"1990","unstructured":"Moses AC, Rosen HN, Moller DE, et al. A point mutation in transthyretin increases affinity for thyroxine and produces euthyroid hyperthyroxinemia. 7 Clin Invest 1990;86:2025-33.","journal-title":"7 Clin Invest"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1677\/joe.0.1290309","article-title":"An inherited nonamyloidogenic transthyretin variant, [Ser61-TTR, with increased thyroxine-binding affinity, characterized by DNA sequencing","volume":"129","author":"Fitch, N.J.S.; Akbari, M.T.; Ramsden, D.B.","year":"1991","unstructured":"Fitch NJS, Akbari MT, Ramsden DB. An inherited nonamyloidogenic transthyretin variant, [Ser61-TTR, with increased thyroxine-binding affinity, characterized by DNA sequencing. J Endocrinol 1991;129:309-13.","journal-title":"J Endocrinol"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1002\/art.1780261211","article-title":"Prealbumin and retinol binding protein serum concentrations in the Indiana type hereditary amyloidosis","volume":"26","author":"Benson, M.D.; Dwulet, F.E.","year":"1983","unstructured":"Benson MD, Dwulet FE. Prealbumin and retinol binding protein serum concentrations in the Indiana type hereditary amyloidosis. Arthritis Rheum 1983;26:1493-8.","journal-title":"Arthritis Rheum"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/0003-2697(83)90304-4","article-title":"Comparison of two methods of high molecular-weight DNA isolation from human leucocytes","volume":"134","author":"Gautreau, C.; Rahuel, C.; Cartron, J.P.; Lucotte, G.","year":"1983","unstructured":"Gautreau C, Rahuel C, Cartron JP, Lucotte G. Comparison of two methods of high molecular-weight DNA isolation from human leucocytes. Anal Biochem 1983;134:320-4.","journal-title":"Anal Biochem"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/j.1399-0004.1990.tb03389.x","article-title":"Hereditary amyloidosis: detection of variant prealbumin genes by restriction enzyme analysis of amplified genomic DNA sequences","volume":"37","year":"1990","unstructured":"Nichols WC, Benson MD. Hereditary amyloidosis: detection of variant prealbumin genes by restriction enzyme analysis of amplified genomic DNA sequences. Clin Genet 1990;37:44-53.","journal-title":"Clin Genet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/0888-7543(89)90020-7","article-title":"Direct sequencing of the gene for Maryland\/German familial amyloidotic polyneuropathy type II and genotyping by allele-specific enzymatic amplification","volume":"5","year":"1989","unstructured":"Nichols WC, Liepnieks JJ, McKusick VA, Benson MD. Direct sequencing of the gene for Maryland\/German familial amyloidotic polyneuropathy type II and genotyping by allele-specific enzymatic amplification. Genomics 1989;5:535-40.","journal-title":"Genomics"},{"key":"ref_8","first-page":"115","article-title":"Identification of carriers of mutant prealbumin gene associated with familial amyloidotic polyneuropathy type I. Study of one Portuguese pedigree","volume":"35","author":"Berriche, S.; Turpin, J.C.; Lucotte, G.","year":"1987","unstructured":"Berriche S, Turpin JC, Lucotte G. Identification of carriers of mutant prealbumin gene associated with familial amyloidotic polyneuropathy type I. Study of one Portuguese pedigree. Prot Biol Fluids 1987;35:115-7.","journal-title":"Prot Biol Fluids"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1399-0004.1990.tb03615.x","article-title":"Diagnosis of familial amyloidotic polyneuropathy in France","volume":"38","year":"1990","unstructured":"Satier F, Nichols WC, Benson MD. Diagnosis of familial amyloidotic polyneuropathy in France. Clin Genet 1990;38:469-73.","journal-title":"Clin Genet"},{"key":"ref_10","first-page":"603","article-title":"Clinical characterization of a new TTR variant in an Italian family: TTR Ala 49. In: Amyloid and amyloidosis","author":"Salvi, F.; Plasmati, R.; Michelucci, R.","year":"1990","unstructured":"Salvi F, Plasmati R, Michelucci R, et al. Clinical characterization of a new TTR variant in an Italian family: TTR Ala 49. In: Amyloid and amyloidosis. Dordrecht: Kluwer Academic Publishers, 1990:603-6."},{"key":"ref_11","first-page":"161","article-title":"Human transthyretin (prealbumin) gene and molecular genetics of familial amyloidotic polyneuropathy","volume":"6","author":"Sakaki, Y.; Yoshioka, K.; Tanahashi, H.; Furuya, H.; Sasaki, H.","year":"1989","unstructured":"Sakaki Y, Yoshioka K, Tanahashi H, Furuya H, Sasaki H. Human transthyretin (prealbumin) gene and molecular genetics of familial amyloidotic polyneuropathy. Mol Biol Med 1989;6:161-8.","journal-title":"Mol Biol Med"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.30.2.120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T04:02:19Z","timestamp":1759723339000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.30.2.120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,2]]},"references-count":11,"journal-issue":{"issue":"2","published-online":{"date-parts":[[1993,2,1]]},"published-print":{"date-parts":[[1993,2]]}},"alternative-id":["10.1136\/jmg.30.2.120"],"URL":"https:\/\/doi.org\/10.1136\/jmg.30.2.120","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,2]]}}}