title: A new lysozyme tyr54asn mutation causing amyloidosis in a family of Swedish ancestry with gastrointestinal symptoms.
abstract: Familial amyloidoses are a group of inherited disorders that cause deposition of misfolded amyloidogenic proteins in various tissues, resulting in organ dysfunction. Point mutations in the coding region of seven different genes are known to cause clinically significant systemic amyloid disease. We describe a new mutation in exon 2 of the lysozyme gene associated with amyloidosis (ALys) in a 61-year-old woman with a 7-year history of non-bloody, watery diarrhea, and weight loss. Biopsies of the duodenum and stomach were positive for amyloid deposits in the lamina propria and blood vessels. Direct DNA sequencing of the lysozyme gene revealed a single base nucleotide transversion from T to A at the first position of codon 54, resulting in replacement of Tyr by Asn in the mature lysozyme protein (pTyr54Asn). Immunoblot analysis of amyloid fibrils extracted from a fat tissue sample confirmed lysozyme as the amyloid protein. Clinically, the phenotype associated with this lysozyme mutation featured chronic abdominal pain, diarrhea, weight loss, malabsorption, and sicca syndrome. There was no associated nephropathy as has been reported for other ALys mutations. We describe a new mutant lysozyme that presents with abdominal discomfort, diarrhea, weight loss, and sicca syndrome.
authors.affiliation: Amyloid Treatment and Research Program, Boston University School of Medicine, MA, USA.
authors.forename: Saulius
authors.initials: S
authors.lastname: Girnius
authors.forename: Martha
authors.initials: M
authors.lastname: Skinner
authors.forename: Brian
authors.initials: B
authors.lastname: Spencer
authors.forename: Tatiana
authors.initials: T
authors.lastname: Prokaeva
authors.forename: Catherine
authors.initials: C
authors.lastname: Bartholomew
authors.forename: Carl
authors.initials: C
authors.lastname: O'Hara
authors.forename: David C
authors.initials: DC
authors.lastname: Seldin
authors.forename: Lawreen H
authors.initials: LH
authors.lastname: Connors
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D028226:Amyloidosis, Familial / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001706:Biopsy; D003967:Diarrhea / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004386:Duodenum / Q000378:metabolism / Q000473:pathology; D005091:Exons; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009113:Muramidase / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D013270:Stomach / Q000473:pathology; D015431:Weight Loss
chemical_list: D000682:Amyloid; D009113:Muramidase