| 1. |
- Gustafson, Lars, et al.
(author)
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A 50-year perspective of a family with chromosome 14-linked Alzheimer’s disease
- 1998
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In: Human Genetics. - : Springer Science and Business Media LLC. - 1432-1203 .- 0340-6717. ; 102:3, s. 253-257
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Journal article (peer-reviewed)abstract
- A Swedish family with two generations suffering from presenile dementia with an unusually severe Alzheimer encephalopathy was first reported in 1946. The hypothesis that the disease was inherited through a dominant gene is strongly supported by the follow-up 50years later of three additional generations and molecular genetic findings of a novel presenilin-1 gene mutation in the family. The pedigree contains six cases with well-documented dementia in four consecutive generations. The Alzheimer encephalopathy was unusually severe in the three cases studied post-mortem, with a pronounced involvement of the central grey structures, such as the claustrum, the nuclei around the third ventricle, the central thalamic nuclei and the brain stem. There were no vascular lesions and little amyloid angiopathy. All six affected cases showed the typical temporoparietal symptom pattern and other core symptoms of Alzheimer’s disease, such as logoclonia, myoclonic twitchings and major motor seizures. Other predominant features were psychomotor slowness, increased muscular tension, a stiff stooped gait and a rapid loss of weight. The symptom pattern is convincingly explained by the consistent and severe involvement of cortical and central grey structures and is probably linked to the presenilin-1 gene mutation.
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| 2. |
- Abrahamson, Magnus, et al.
(author)
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Hereditary cystatin C amyloid angiopathy: Identification of the disease causing mutation and specific diagnosis by polymerase chain reaction based analysis
- 1992
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In: Human Genetics. - 1432-1203. ; 89:4, s. 377-380
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Journal article (peer-reviewed)abstract
- Hereditary cystatin C amyloid angiopathy (HCCAA) is a dominantly inherited disease characterized by amyloidosis, dementia and fatal cerebral hemorrhage of young adults. A method for rapid and simple diagnosis of HCCAA is described. It is based upon oligonucleotide-directed enzymatic amplification of a 275-bp genomic DNA segment containing exon 2 of the cystatin C gene from a blood sample, followed by digestion of the amplification product with AluI. Loss of an AluI recognition site in the amplified DNA segment from HCCAA patients results in a deviating band-pattern at agarose gel electrophoresis, compared with that obtained from normal subjects or unaffected HCCAA family members. In a population of 9 patients with manifest HCCAA, 14 patients with other causes of brain hemorrhage and 16 healthy individuals, the diagnostic procedure displayed a sensitivity and specificity for HCCAA of 100%. Amplified DNA segments from 4 HCCAA patients of four different families were analyzed by nucleotide sequencing; the HCCAA-causing mutation in all families was found to be a single TrarrA substitution in the codon for amino acid residue 68 of cystatin C.
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| 3. |
- Abrahamson, Magnus, et al.
(author)
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The human cystatin C gene (CST3), mutated in hereditary cystatin C amyloid angiopathy, is located on chromosome 20
- 1989
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In: Human Genetics. - 1432-1203. ; 82:3, s. 223-226
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Journal article (peer-reviewed)abstract
- Hereditary cystatin C amyloid angiopathy has recently been shown to be caused by a point mutation in the cystatin C gene. To determine the chromosomal localization of the gene, 20 human-rodent somatic cell hybrids and a fulllength cystatin C cDNA probe were used. Southern blot analysis of BamHI digested cell hybrid DNA revealed that the probe recognizes a 10.6 kb human specific fragment and that this fragment cosegregates with human chromosome 20. Therefore, the human cystatin C gene (CST3) was assigned to chromosome 20.
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| 4. |
- Balbin, Milagros, et al.
(author)
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A novel mutation in the β-protein coding region of the amyloid β-protein precursor (APP) gene
- 1992
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In: Human Genetics. - 1432-1203. ; 89:5, s. 580-582
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Journal article (peer-reviewed)abstract
- A novel mutation, a C to T transition at base pair 2124 in exon 17 of the amyloid beta-protein precursor (APP) gene, has been identified by direct sequencing of amplified DNA from two Alzheimer's disease (AD) patients. A simple oligonucleotide-hybridization procedure was developed to allow population studies of this DNA variation. The mutation, which is silent at the protein level, was present in 2 out of 12 investigated AD patients, in 1 out of 60 non-AD patients and in 1 out of 30 healthy individuals. The mutation can be used as a new marker for linkage studies involving the APP gene, although more comprehensive population studies are required to determine the status of the mutation as a possible risk factor for the development of AD.
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| 5. |
- Balbin, Milagros, et al.
(author)
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A sequence variation in the human cystatin D gene resulting in an amino acid (Cys/Arg) polymorphism at the protein level
- 1993
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In: Human Genetics. - 1432-1203. ; 90:6, s. 668-669
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Journal article (peer-reviewed)abstract
- A polymorphism in the coding region of the human cystatin D gene has been detected by direct sequencing of amplified DNA from different individuals. The variation, resulting from a T/C transition in exon 1 of the gene, causes an amino acid variation, Cys/Arg, at the protein level. An allele-specific oligonucleotide hybridization assay was developed and used to demonstrate this polymorphism in the population. The deduced frequencies were 0.55 and 0.45 for the Cys and Arg variant-encoding alleles, respectively.
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| 6. |
- Balbin, Milagros, et al.
(author)
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An Ala/Thr variation in the coding region of the human cystatin C gene (CST3) detected as a Sst II polymorphism
- 1993
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In: Human Genetics. - 1432-1203. ; 92:2, s. 206-207
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Journal article (peer-reviewed)abstract
- A DNA variation in the coding region of the human cystatin C gene has been detected by direct sequencing. The polymorphism, a G/A transition, leads to an Ala/Thr variation in the penultimate amino acid of the signal peptide. The base substitution results in the loss of a SstII restriction site, thus allowing the design of a rapid polymerase chain reaction assay for analysis of this polymorphism in the population.
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| 7. |
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| 8. |
- Balbin, Milagros, et al.
(author)
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Sst II polymorphic sites in the promoter region of the human cystatin C gene
- 1991
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In: Human Genetics. - 1432-1203. ; 87:6, s. 751-752
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Journal article (peer-reviewed)abstract
- By direct sequencing of polymerase chain reaction (PCR) amplified DNA from different individuals, three point mutations have been found in a 220-bp fragment from the promoter region of the human cystatin C gene. The three mutations are all localized within a short segment of 85 bp on the same allele. One of the base substitutions results in the generation of a novel SstII restriction site and another in the loss of the commonly occurring SstII restriction site. A PCR-based assay for analysis of the two SstII sites was designed and used to demonstrate Mendelian inheritance of the polymorphism. This SstII restriction fragment lenght polymorphism offers a new probe-independent marker for chromosome 20 linkage studies.
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| 9. |
- Ekström, Ulf, et al.
(author)
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An efficient screening procedure detecting six novel mutations in the LDL receptor gene in Swedish children with hypercholesterolemia
- 1995
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In: Human Genetics. - 1432-1203. ; 96:2, s. 147-150
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Journal article (peer-reviewed)abstract
- Familial hypercholesterolemia (FH) is an autosomal semi-dominant disorder caused by defects in the low density lipoprotein receptor (LDLR) gene and is a well-documented risk factor for developing cardiovascular disease. The LDLR genes of five Swedish children with FH were examined in this study. Initial mutation screening was performed by denaturing gradient gel electrophoresis (DGGE) with enzymatically amplified exon-sized fragments, each containing a tailing GC-rich requence. The GC-clamped fragments had been synthesized with a restriction site adjacent to the intron-corresponding sequence to allow detachment of the clamps, thereby rendering the fragments suitable for subsequent analysis by single-strand conformation polymorphism (SSCP) analysis of samples from patients with no DGGE-detectable mutations. In addition, all the LDLR genes of the patients were screened for large alterations by restriction fragment length polymorphism analysis. Following this strategy, seven different, potentially disease-causing mutations were detected in the five children with FH. Six of the alterations, five single-base substitutions and one dinucleotide deletion, have not previously been described. DGGE detected six of the mutations and SSCP the seventh.
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