Codon 618 variant of Alzheimer amyloid gene associated with inherited cerebral hemorrhage

Ann Neurol. 1991 Nov;30(5):730-3. doi: 10.1002/ana.410300516.

Abstract

Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D) is an autosomal dominant form of severe cerebrovascular amyloid angiopathy causing recurrent strokes during the fifth and sixth decades of life. The major constituent of the amyloid deposits in HCHWA-D is the amyloid beta-protein (A beta), also found in Alzheimer's disease. A point mutation in the DNA sequence encoding A beta has been found in 2 unrelated patients with HCHWA-D, and an assay detecting the single base change was developed for diagnostic purposes. We describe the detection of the point mutation in a patient living in the United States, suffering from recurring cerebral hemorrhages, who only recently was diagnosed with HCHWA-D. In addition, we tested a number of family members, and found the mutation in 2 additional individuals, one of them too young to exhibit clinical manifestations. This study combined with the study of two other families in Holland indicates that the codon 618 variant in the amyloid precursor protein gene segregates with HCHWA-D.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Amyloid beta-Peptides / genetics*
  • Anxiety Disorders / diagnosis
  • Cerebral Amyloid Angiopathy / complications
  • Cerebral Amyloid Angiopathy / ethnology
  • Cerebral Amyloid Angiopathy / genetics*
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / diagnosis
  • Cerebral Hemorrhage / genetics*
  • Codon
  • DNA Mutational Analysis
  • Diagnostic Errors
  • Female
  • Humans
  • Middle Aged
  • Netherlands / ethnology
  • Pedigree
  • Recurrence
  • Syncope / etiology

Substances

  • Amyloid beta-Peptides
  • Codon