title: Prevalence of germline mutations in the TTR gene in a consecutive series of surgical pathology specimens with ATTR amyloid.
abstract: Transthyretin-derived amyloidosis (ATTR) amyloidosis is the third most prevalent amyloid type in surgical pathology and may occur as a hereditary disease with germline mutations in the TTR gene or as senile systemic amyloidosis (SSA) without mutations. Distinction between hereditary ATTR amyloidosis and SSA is of central importance, as the former necessitates genetic counseling and can be treated by liver transplantation. However, little is known about the prevalence of hereditary ATTR amyloidosis in surgical pathology specimens. We have examined the distribution of hereditary ATTR amyloidosis and SSA in a consecutive series of surgical pathology specimens with histologically and immunohistochemically confirmed ATTR amyloid. Thirty-three consecutive patients were retrieved from the Amyloid Registry of the Charité University Hospital. Genomic DNA was extracted from formalin-fixed and paraffin-embedded tissue or patient blood and examined by DNA sequencing. ATTR amyloid was found in the gastrointestinal tract, endomyocardium, peripheral nerve, carpal tunnel ligament, synovia, breast, and testicle. Amyloid fibrils were present as interstitial and vascular deposits, as evidenced by Congo red staining. TTR gene mutations were detected in 12 of 30 patients, with p.Val30Met being the most prevalent (5 patients). Furthermore, 2 novel mutations (p.Asp39Val and p.Glu54Asp) were found. In patients carrying a mutation, ATTR amyloid was found in the gastrointestinal tract, myocardium, nerve, and testicles. To conclude, the hereditary form of ATTR amyloid seems to be more common in elderly patients than previously thought. It is, therefore, important to genetically test every patient when diagnosing ATTR amyloidosis.
authors.affiliation: Department of Pathology, Medical Clinic of Gastroenterology, Hepatology, and Endocrinology, Charité University Hospital, Berlin, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Eriksson
authors.forename: Janine
authors.initials: J
authors.lastname: Büttner
authors.forename: Theodor
authors.initials: T
authors.lastname: Todorov
authors.forename: Saniye
authors.initials: S
authors.lastname: Yumlu
authors.forename: Stefan
authors.initials: S
authors.lastname: Schönland
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.forename: Arnt V
authors.initials: AV
authors.lastname: Kristen
authors.forename: Thomas
authors.initials: T
authors.lastname: Dengler
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Burkhard
authors.initials: B
authors.lastname: Helmke
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schmidt
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
mesh_terms: D000328:Adult; D017677:Age Distribution; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000378:metabolism*; D028226:Amyloidosis, Familial / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011228:Prealbumin / Q000235:genetics*; D015995:Prevalence; D017678:Sex Distribution
chemical_list: D000682:Amyloid; D011228:Prealbumin