| 1. |
- Arkblad, Eva L, et al.
(författare)
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Multiplex ligation-dependent probe amplification improves diagnostics in spinal muscular atrophy
- 2006
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Ingår i: Neuromuscular disorders : NMD. - : Elsevier BV. - 0960-8966 .- 1873-2364. ; 16:12, s. 830-8
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Tidskriftsartikel (refereegranskat)abstract
- Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by decreased levels of survival motor neuron protein (SMN). In the majority of cases, this decrease is due to absence of the SMN1 gene. Multiplex ligation-dependent probe amplification (MLPA) is a modern quantitative molecular method. Applied in SMA cases, it improves diagnostics by simultaneously identifying the number of copies of several target sequences in the SMN1 gene and in nearby genes. Using MLPA in clinical diagnostics, we have identified a previously unreported, partial deletion of SMN1 (exons 1-6) in two apparently unrelated Swedish families. This mutation would not have been detected by conventional diagnostic methods. This paper illustrates the broad clinical and genetic spectrum of SMA and includes reports of MLPA results and clinical descriptions of a patient with homozygous absence of SMN1 and only one SMN2 (prenatal onset SMA type 1), an asymptomatic woman with five SMN2 (lacking SMN1) and representative patients with SMA types 1, 2 and 3.
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| 2. |
- Entesarian, Miriam, et al.
(författare)
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A chromosome 10 variant with a 12 Mb inversion [inv(10)(q11.22q21.1)] identical by descent in the Swedish population
- 2009
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Ingår i: American Journal of Medical Genetics. - : Wiley Interscience. - 0148-7299 .- 1096-8628 .- 1552-4825 .- 1552-4833. ; 149A:3, s. 380-386
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Tidskriftsartikel (refereegranskat)abstract
- We identified a paracentric inversion of chromosome 10 [inv(10)(q11.22q21.1)] in 0.20% of Swedish individuals (15/7,439) referred for cytogenetic analysis. A retrospective analysis of 8,896 karyotypes from amniocenteses in Sweden revealed a carrier frequency of 0.079% (7/8,896) for the inversion. Cloning and detailed analysis of the inversion breakpoint regions show enrichment for interspersed repeat elements and AT-stretches. The centromeric breakpoint coincides with that of a predicted inversion from HapMap data, which suggests that this region is involved in several chromosome 10 variants. No known gene or predicted transcript are disrupted by the inversion which spans approximately 12 Mb. Carriers from four non-related Swedish families have identical inversion breakpoints and haplotype analysis confirmed that the rearrangement is identical by descent. Diagnosis was retrieved in 6 out of the 15 carriers referred for cytogenetic analysis. No consistent phenotype was found to be associated with the inversion. Our study demonstrates that the inv(10)(q11.22q21.1) is a rare and inherited chromosome variant with a broad geographical distribution in Sweden.
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| 3. |
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| 4. |
- Örlén, Hanna, et al.
(författare)
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SPG11 mutations cause Kjellin syndrome, a hereditary spastic paraplegia with thin corpus callosum and central retinal degeneration.
- 2009
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Ingår i: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. - : Wiley. - 1552-485X .- 1552-4841. ; 150B:7, s. 984-992
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Tidskriftsartikel (refereegranskat)abstract
- Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is genetically heterogenous and approximately 35% of patients carry mutations in either of the SPG11 or SPG15 genes. Disease onset is during the first three decades of life with spastic paraplegia and mental impairment. Peripheral neuropathy and amyotrophy may occur. Kjellin syndrome is characterized by central retinal degeneration in addition to ARHSP-TCC and the disease is associated with mutations in the SPG15 gene. We identified five patients in four unrelated kindreds with spastic paraplegia and mental impairment. Magnetic resonance imaging revealed TCC, atrophy elsewhere in the brain and increased T2 signal intensity in the periventricular white matter. Probands from the four kindreds were screened for mutations in the SPG11 gene. All patients were found homozygous or compound heterozygous for truncating SPG11 mutations of which four are reported for the first time. Ophthalmological investigations revealed that the four index cases have central retinal degeneration consistent with Kjellin syndrome. PET examinations with N-[11C-methyl]-L-deuterodeprenyl (DED) and fluor-18 2-fluorodeoxyglucose (FDG) were performed in two patients with Kjellin syndrome. We observed a reduced glucose uptake in the thalami, anterior cingulum, and sensorimotor cortex indicating neuronal loss, and an increased DED binding in the thalami and pons which suggests astrogliosis. From our results we extend the SPG11 associated phenotype to comprise also Kjellin syndrome, previously found to be associated with mutations in the SPG15 gene. We anticipate that degeneration of the central retina is a common and previously unrecognized feature in SPG11 related disease.
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| 5. |
- Berglund, Eva C., et al.
(författare)
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Run-off replication of host-adaptability genes is associated with gene transfer agents in the genome of mouse-infecting Bartonella grahamii
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:7, s. e1000546-
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Tidskriftsartikel (refereegranskat)abstract
- The genus Bartonella comprises facultative intracellular bacteria adapted to mammals, including previously recognized and emerging human pathogens. We report the 2,341,328 bp genome sequence of Bartonella grahamii, one of the most prevalent Bartonella species in wild rodents. Comparative genomics revealed that rodent-associated Bartonella species have higher copy numbers of genes for putative host-adaptability factors than the related human-specific pathogens. Many of these gene clusters are located in a highly dynamic region of 461 kb. Using hybridization to a microarray designed for the B. grahamii genome, we observed a massive, putatively phage-derived run-off replication of this region. We also identified a novel gene transfer agent, which packages the bacterial genome, with an over-representation of the amplified DNA, in 14 kb pieces. This is the first observation associating the products of run-off replication with a gene transfer agent. Because of the high concentration of gene clusters for host-adaptation proteins in the amplified region, and since the genes encoding the gene transfer agent and the phage origin are well conserved in Bartonella, we hypothesize that these systems are driven by selection. We propose that the coupling of run-off replication with gene transfer agents promotes diversification and rapid spread of host-adaptability factors, facilitating host shifts in Bartonella.
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| 6. |
- Casper, C, et al.
(författare)
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Coreceptor usage of primary HIV type 1 isolates obtained from different lymph node subsets
- 2005
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Ingår i: AIDS Research and Human Retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 21:12, s. 1003-1010
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Tidskriftsartikel (refereegranskat)abstract
- Biological characteristics of virus quantitatively rescued from different cell types present in lymph nodes of HIV-1-infected individuals in various stages of their disease were determined, not including patients with AIDS defining illness. Viruses were obtained by cocultivation with donor monocyte-derived macrophages and T-lymphocytes and their biological phenotype compared to viruses obtained from the peripheral blood mononuclear cells of the same patient. The biological phenotype was determined on established cell lines (U937-2, CEM, and MT-2) and on the U87.CD4 coreceptor indicator cell lines and variable region 3 (V3) of the envelope was subjected to direct sequencing. All isolates obtained from lymph node subsets used CCR5 as coreceptor. Furthermore, these viruses were also sensitive to inhibition by beta-chemokines as analyzed for viruses of one patient. All 12 V3 regions showed a unique sequence indicating compartmentalization within each patient. The biological phenotype of CCR5-dependent (R5) HIV-1 isolates obtained from PBMC resembles the phenotype of viruses isolated from different lymph node cell subsets.
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| 7. |
- Ehrenborg, Christian, 1970-
(författare)
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Bartonella Infections in Sweden: : Clinical Investigations and Molecular Epidemiology
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Characteristically, in infections that are caused by the zoonotic pathogen Bartonella naturally infected reservoir hosts are asymptomatic, where infected incidental, non-natural, hosts develop symptomatic disease. Cat-scratch disease (CSD) is a well known example. Bartonella infections in humans may be self-limiting or fulminant and affect different organ systems. The objectives of the present thesis were to (1) identify and characterise Bartonella infection cases in Sweden, (2) to investigate certain human populations regarding Bartonella infections, and (3) compare natural populations of different Bartonella species. Cases with typical and atypical CSD were recognised by using a combination of PCR and serology. Gene sequence comparisons of different genes in B. henselae isolates from the United States and Europe showed that ftsZ gene variation is a useful tool for Bartonella genotyping. Myocarditis was a common finding among Swedish elite orienteers succumbing to sudden unexpected cardiac death (SUCD). The natural cycle of Bartonella spp., the life style of orienteers, elevated antibody titres to Bartonella antigens, Bartonella DNA amplified from myocardium and the lack of another feasible explanation make Bartonella a plausible aetiological factor. The first reported case of Bartonella endocarditis (B. quintana) was identified in an immunocompromised patient who underwent heart valve replacement. The patient had been body louse-infested during his childhood. It is hypothesised that a chronic B. quintana infection was activated by the immunosuppression. There was no evidence of an ongoing trench fever (TF) epidemic in a Swedish homeless population, although an increased risk for exposure to Bartonella antigens was demonstrated. The lack of louse infestation might explain the absence of B. quintana bacteremia and low B. quintana antibody titres. Comparisons of genetic loci and the whole genomes of environmental B. grahamii isolates from the Uppsala region, Sweden displayed variants that were not related to specific host species but to geographic locality. Natural boundaries seemed to restrict gene flow.
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| 8. |
- Ehrenborg, Christian, et al.
(författare)
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High Bartonella spp. seroprevalence in a Swedish homeless population but no evidence of trench fever
- 2008
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 40:3, s. 208-215
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Tidskriftsartikel (refereegranskat)abstract
- Blood samples and epidemiological data were collected from 50 homeless patients in central Stockholm, Sweden. Sera were analysed for antibodies to B. henselae, B. quintana, B. elizabethae and B. grahamii. Whole blood was cultured and used as substrate for a newly developed quantitative real time polymerase chain reaction (QPCR) specifically targeting Bartonella spp. DNA. 61 matched blood donor sera were used as controls. Homeless patients were significantly more often seropositive to Bartonella spp. than controls (OR 7.58 (3.30-17.39), p<0.05). Reactivity to the B. elizabethae antigen was dominating, although the difference between patients and controls was most significant in seroreactivity to the B. henselae antigen. There was no evidence of an ongoing B. quintana epidemic. The absence of louse infestation could explain the lack of B. quintana bacteraemia and the failure to amplify Bartonella DNA.
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| 9. |
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| 10. |
- Hamberg, Eva, et al.
(författare)
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Försonad mångfald
- 2006
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Bok (populärvet., debatt m.m.)
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