Rapidly progressive amyloid polyneuropathy associated with a novel variant transthyretin serine 25.
We report a 52-year-old woman with a novel transthyretin (TTR) variant serine replacing alanine at residue 25 [Ala25Ser (Serine 25)], who showed a unique clinical picture with a relatively acute onset neuropathy within a few days of an influenza vaccination, progressing to a severe degree within 2 years. Sural nerve biopsy revealed amyloid deposition in the endoneurium. Sequencing of the proband's DNA revealed a G to T transversion at the first position of codon 25 of TTR gene. DNA analysis of this family showed the same mutation in her older sister and a niece, but her parents did not have the mutation. Haplotype analysis revealed the mutation to be clearly linked to haplotype III allele inherited from the proband's father. These results indicate this novel Serine 25 mutation originated in the paternal germline mosaicism. It is possible that the vaccination had an influence on the unique clinical picture, but this remains uncertain.
Yazaki
Masahide
M
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 975 West Walnut Street, IB-503, Indianapolis, Indiana 46202, USA.
Yamashita
Taro
T
Kincaid
John C
JC
Scott
John R
JR
Auger
Raymond G
RG
Dyck
Peter J
PJ
Benson
Merrill D
MD
D000595:Amino Acid Sequence / Q000235:genetics; D000682:Amyloid / Q000378:metabolism; D028227:Amyloid Neuropathies, Familial / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence / Q000235:genetics; D004247:DNA / Q000235:genetics; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D011228:Prealbumin / Q000235:genetics*; D013497:Sural Nerve / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D000682:Amyloid; D011228:Prealbumin; D004247:DNA