DNA diagnosis for hereditary cerebral hemorrhage with amyloidosis (Dutch type)
Hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D) is tightly linked to the Alzheimer amyloid precursor protein gene on chromosome 21, which codes for the amyloid beta-protein. A point mutation detected at position 1852 of the amyloid precursor protein gene in four HCHWA-D patients was hypothesized to be the basic defect. This study proves that 22 HCHWA-D patients from three pedigrees all carry this point mutation, whereas the mutation is absent in escapees from the HCHWA-D families as well as in randomly selected Dutch individuals. A mutation-specific oligonucleotide is now available for the confirmation of the HCHWA-D diagnosis. Therefore, presymptomatic testing and prenatal evaluation of individuals at risk in the HCHWA-D families is now feasible.
Department of Human Genetics, Sylvius Laboratory, Leiden University, The Netherlands.
E
E
Bakker
C
C
van Broeckhoven
J
J
Haan
E
E
Voorhoeve
W
W
van Hul
E
E
Levy
I
I
Lieberburg
M D
MD
Carman
G J
GJ
van Ommen
B
B
Frangione
D000368:Aged; D016229:Amyloid beta-Peptides / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor; D000686:Amyloidosis / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D001483:Base Sequence; D002543:Cerebral Hemorrhage / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D002891:Chromosomes, Human, Pair 21; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009426:Netherlands; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011498:Protein Precursors / Q000235:genetics*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D011498:Protein Precursors