title: Hereditary apolipoprotein AI-associated amyloidosis in surgical pathology specimens: identification of three novel mutations in the APOA1 gene.
abstract: Apolipoprotein AI-derived (AApoAI) amyloidosis may present either as a non-hereditary form with wild-type protein deposits in atherosclerotic plaques or as a hereditary form due to germline mutations in the APOA1 gene. Currently, more than 50 apoAI variants are known, and 13 are associated with amyloidosis. We describe six patients with AApoAI amyloidosis due to APOA1 germline mutations that affect the larynx, small intestine, large intestine, heart, liver, kidney, uterus, ovary, or pelvic lymph nodes. In each patient, the amyloid showed a characteristic apple green birefringence when viewed under polarized light after Congo red staining and was immunoreactive with antibodies against apoAI. Sequence analyses revealed one known (p.Leu75Pro) and three novel APOA1 mutations that included gene variations leading to two different frameshifts (p.Asn74fs and p.Ala154fs) and one amino acid exchange (p.Leu170Pro). These three novel mutations extend our knowledge about both the location of the mutations and the organ distribution in hereditary AApoAI amyloidosis. Thirteen of the now sixteen amyloidogenic mutations are localized in two hot-spot regions that span residues 50 to 93 and 170 to 178. The organ distribution and clinical presentation of AApoAI amyloidosis seems to depend on the position of the mutation. Patients with alterations in codons 1 to 75 mostly develop hepatic and renal amyloidosis, while carriers of mutations in residues 173 to 178 mainly suffer from cardiac, laryngeal, and cutaneous amyloidosis.
authors.affiliation: Department of Pathology, Charité University Hospital, Berlin, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Eriksson
authors.forename: Stefan
authors.initials: S
authors.lastname: Schönland
authors.forename: Saniye
authors.initials: S
authors.lastname: Yumlu
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.forename: Hanna
authors.initials: H
authors.lastname: von Hutten
authors.forename: Zarina
authors.initials: Z
authors.lastname: Gioeva
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Janine
authors.initials: J
authors.lastname: Büttner
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schmidt
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken