ATTR amyloid in the carpal tunnel ligament is frequently of wildtype transthyretin origin.

The carpal tunnel ligament often encloses transthyretin-derived (ATTR) amyloid deposits. In this study we tested the hypothesis that ATTR amyloid in the carpal tunnel ligament is most commonly of wildtype origin in a Caucasian population without endemic background of familial amyloid polyneuropathy. All resection specimens from the carpal tunnel ligament were retrieved from the Amyloid Registry of the University of Kiel spanning the period of 2004-2011 and dichotomized into two study groups: the first study group of 25 patients was obtained from diverse referring pathologists. The second group comprised a patient cohort of 73 patients obtained from a single-referring department of pathology. The selection of biopsies was based on the histological identification of amyloid by Congo red staining and polarization microscopy between crossed polars and immunohistochemical classification as ATTR amyloid. A novel anti-TTR-peptide antibody was raised in rabbits using a recombinant peptide (FHEHAEVVFTANDSGPRRYT) spanning residues 87-106 of the TTR protein. Amplification of the TTR exons 1, 2, 3 and 4 was done by a nested polymerase chain reaction approach. Ninety-eight biopsies were available from 98 patients, including 51 women and 47 men. All amyloid deposits showed strong immunoreactions with the novel anti-TTR peptide antibody. In 81 of 98 patients, genomic DNA was available. In 10 (12%) patients non-amyloidogenic TTR gene mutations were found with the following amino acid substitutions: p.G6S (normal allelic variant). A single patient carried a p.G6S and a p.M13I-variant. The remaining patients all showed wildtype sequence of the TTR gene (70 patients). No significant difference was found between the two study groups. ATTR amyloid in the carpal tunnel ligament is commonly of wildtype origin and genetic counseling is not mandatory in these patients.