title: New transthyretin variants SER 91 and SER 116 associated with familial amyloidotic polyneuropathy. Mutations in brief no. 151. Online.
abstract: Mutations of the transthyretin (TTR) gene are associated with familial amyloidotic polyneuropathy (FAP). Two new mutations were detected in French patients with TTR amyloidosis. The first patient was a 72 year old man who presented with severe and rapidly evolving sensory motor polyneuropathy of the 4 limbs, a bilateral carpal tunnel syndrome and a restrictive cardiomyopathy. His father died after a clinical history suggestive in retrospect of TTR amyloidosis. The second patient was a 75 year old man who presented with axonal sensory neuropathy of the 4 limbs and a bilateral carpal tunnel syndrome. In both cases immunohistochemistry performed on a nerve biopsy reveled TTR positive amyloid. Direct genomic sequencing of the full TTR gene coding region indicated two heterozygous transversions encoding Ser for Ala 91 substitution in the third exon of the gene in patient 1 and Ser for Tyr 116 substitution in the fourth exon of the gene in patient 2. The mutations were confirmed by digesting PCR products with restriction enzymes and were not found in a control population of 100 unrelated individuals. The Ser 116 substitution was also detected in the daughter and the 70 year old sister of the proband. However the absence of symptomatology suggestive of TTR amyloidosis may be related to the late onset of the disease. The clinical immunohistochemical and molecular studies in both patients are highly suggestive of an association between the Ser 91 and Ser 116 TTR variants with amyloidosis.
authors.affiliation: Laboratoire d'Hormonologie et Biologie Moléculaire, I.F.R 21, Hôpital de Bicêtre, 94275 Le Kremlin Bicêtre, France. misrahi@infobiogen.fr
authors.forename: A M
authors.initials: AM
authors.lastname: Misrahi
authors.forename: V
authors.initials: V
authors.lastname: Plante
authors.forename: T
authors.initials: T
authors.lastname: Lalu
authors.forename: L
authors.initials: L
authors.lastname: Serre
authors.forename: D
authors.initials: D
authors.lastname: Adams
authors.forename: D C
authors.initials: DC
authors.lastname: Lacroix
authors.forename: G
authors.initials: G
authors.lastname: Saïd
mesh_terms: D000368:Aged; D000409:Alanine; D017772:Amyloid Neuropathies / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D011228:Prealbumin / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics*; D012694:Serine; D014443:Tyrosine
chemical_list: D011228:Prealbumin; D020033:Protein Isoforms; D014443:Tyrosine; D012694:Serine; D000409:Alanine