An unusual transthyretin gene missense mutation (TTR Phe33Val) linked to familial amyloidotic polyneuropathy.
Familial amyloidotic polyneuropathy is a rare autosomal dominant disease, with clinical symptoms beginning in most kindreds within the third to seventh decades of life. The primary defect results from one of a number of mutations in the transthyretin (TTR) gene. Over 80 mutations in the TTR gene have been described. Most mutations give rise to adult onset progressive peripheral and autonomic neuropathy, due to amyloid deposition within the nerves, and often subclinical cardiac amyloid and vitreous deposits. We report here the clinical and molecular characterization of a rare TTR missense mutation discovered in a young woman from Macedonia, showing severe axonal sensory-motor polyneuropathy, restrictive cardiomyopathy and bilateral vitreous deposits. The transthyretin gene, analyzed by direct nucleotide sequencing, demonstrated a T to G transversion at nucleotide 183 in the exon 2 which is predicted to cause a heterozygous valine for phenylalanine substitution at codon 33 (TTR Phe33Val). This mutation has been previously reported only twice, without complete clinical descriptions.
Department of Neuroscience and Biomedical Technologies, University of Milano-Bicocca, Monza, Italy.
Roberta
R
Frigerio
Gian Maria
GM
Fabrizi
Moreno
M
Ferrarini
Tiziana
T
Cavallaro
Laura
L
Brighina
Patrizia
P
Santoro
Elio
E
Agostoni
Guido
G
Cavaletti
Nicolò
N
Rizzuto
Carlo
C
Ferrarese
D000328:Adult; D028227:Amyloid Neuropathies, Familial / Q000235:genetics* / Q000473:pathology; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D011228:Prealbumin / Q000235:genetics* / Q000378:metabolism; D013497:Sural Nerve / Q000378:metabolism / Q000473:pathology*
D011228:Prealbumin