| 1. |
- Abel, Frida, 1974, et al.
(författare)
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Gain of chromosome arm 17q is associated with unfavourable prognosis in neuroblastoma, but does not involve mutations in the somatostatin receptor 2(SSTR2) gene at 17q24.
- 1999
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 81:8, s. 1402-9
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Tidskriftsartikel (refereegranskat)abstract
- Deletion of chromosome arm 1p and amplification of the MYCN oncogene are well-recognized genetic alterations in neuroblastoma cells. Recently, another alteration has been reported; gain of the distal part of chromosome arm 17q. In this study 48 neuroblastoma tumours were successfully analysed for 17q status in relation to known genetic alterations. Chromosome 17 status was detected by fluorescence in situ hybridization (FISH). Thirty-one of the 48 neuroblastomas (65%) showed 17q gain, and this was significantly associated with poor prognosis. As previously reported, 17q gain was significantly associated with metastatic stage 4 neuroblastoma and more frequently detected than both deletion of chromosome arm 1p and MYCN amplification in tumours of all stages. 17q gain also showed a strong correlation to survival probability (P = 0.0009). However, the most significant correlation between 17q gain and survival probability was observed in children with low-stage tumours (stage 1, 2, 3 and 4S), with a survival probability of 100% at 5 years from diagnosis for children with tumours showing no 17q gain compared to 52.5% for those showing 17q gain (P = 0.0021). This suggests that 17q gain as a prognostic factor plays a more crucial role in low-stage tumours. Expression of the somatostatin receptor 2 (SSTR2), localized in chromosome region 17q24, has in previous studies been shown to be positively related to survival in neuroblastoma. A point mutation in the SSTR2 gene has earlier been reported in a human small-cell lung cancer. In this study, mutation screening of the SSTR2 gene in 43 neuroblastoma tumours was carried out with polymerase chain reaction-based single-stranded conformation polymorphism/heteroduplex (SSCP/HD) and DNA sequencing, and none of the tumours showed any aberrations in the SSTR2 gene. These data suggest that mutations in the SSTR2 gene are uncommon in neuroblastoma tumours and do not correlate with either the 17q gain often seen or the reason some tumours do not express SSTR2 receptors. Overall, this study indicates that gain of chromosome arm 17q is the most frequently occurring genetic alteration, and that it is associated with established prognostic factors.
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| 2. |
- Enerbäck, Charlotta, 1965, et al.
(författare)
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Cytogenetic analysis of 477 psoriatics revealed an increased frequency of aberrations involving chromosome region 11q
- 1999
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Ingår i: Eur J Hum Genet. ; 7:3, s. 339-44
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is an inflammatory skin disorder affecting approximately 3% of the population. Genetic studies published so far have shown a complex genetic inheritance with heterogeneity and a putative major susceptibility locus in the HLA region on chromosome 6. We have collected a large amount of material consisting mostly of small nuclear families in order to perform a genome-wide scan for psoriasis-associated genes. In order to focus the scan properly on possible candidate regions, we performed a cytogenetic analysis of 477 unrelated psoriatics. We divided our findings into sporadic, affecting a minor fraction of the cells, and constitutional, i.e. they were present in all cells examined. We found three cases of balanced translocation, all of which involved chromosome 11q. Two of these had a breakpoint in q12-13, whilst one involved the telomeric part of chromosome 11q. In order to characterise further the breakpoint on 11q12-13, we used bacterial artificial chromosomes (BACs) analysed by fluorescent in situ hybridisation (FISH). We were able to show that the persons had a close, but not identical breakpoints; they were separated by at least 5 cM. The major atopy locus is located in this region, as well as a locus for insulin-dependent diabetes mellitus, both being conditions with a pathogenetic mechanism involving antigen presentation.
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| 3. |
- Enerbäck, Charlotta, 1965, et al.
(författare)
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Evidence that HLA-Cw6 determines early onset of psoriasis, obtained using sequence-specific primers (PCR-SSP)
- 1997
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Ingår i: Acta Derm Venereol. ; 77:4, s. 273-6
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis vulgaris has previously been shown to associate with certain HLA alleles. HLA-Cw6 is considered to be the primary association, based on calculations of relative risk after serological typing. This association is reportedly more pronounced in early- than in late-onset psoriasis. We performed a PCR-based typing with sequence-specific primers, which has been shown to give a more complete result than serology. Two hundred and one unrelated patients with psoriasis, with a mean age of 40 years, and 77 healthy controls were typed. Two thirds (67%) of the patients were positive for one or two copies of the allele, while the corresponding figure for the control group was 12%. A significant peak for age at onset of 21 or younger was seen for the Cw6 carriers. For patients older than 21 at onset, the frequency of Cw6 was significantly lower; e.g. for patients with an age at onset between 30 and 35 the frequency was comparable to the level of the control group. The high frequency of Cw6 among patients with an age at onset of 21 or younger is in agreement with data of other groups. In comparison with this age-at-onset group the frequency of Cw6 is sharply reduced among patients with an age at onset of 22 years or older, which contrasts with earlier studies. This may reflect differences between population groups but may also be due to the higher sensitivity of the PCR-based HLA-Cw6 typing method. In view of these findings, we suggest that psoriasis is a genetically determined disease, in which the additional presence of HLA-Cw6 is associated with the characteristic of early onset.
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| 4. |
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| 5. |
- Enlund, Fredrik, 1968, et al.
(författare)
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Analysis of three suggested psoriasis susceptibility loci in a large Swedish set of families: confirmation of linkage to chromosome 6p (HLA region), and to 17q, but not to 4q
- 1999
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Ingår i: Hum Hered. ; 49:1, s. 2-8
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is known to be a heterogeneous disease with so far three reported major psoriasis susceptibility loci on chromosome 4q, 6p and 17q. In this study we investigated three reported gene locations by nonparametric and parametric linkage analysis in a large family set consisting of 104 families (153 sib pairs) from Sweden. We could confirm linkage to chromosome 6p. A maximum heterogeneous lod score of 2.78 was reached at locus D6S276 (alpha = 0.60). Allelic association studies within the HLA region indicated linkage disequilibrium at locus TNFbeta with a significant p value of 0.0009. Furthermore, we obtained weak evidence of linkage to the locus on chromosome 17q while no evidence of linkage could be found to the chromosome 4q region.
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| 6. |
- Enlund, Fredrik, 1968, et al.
(författare)
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Psoriasis susceptibility locus in chromosome region 3q21 identified in patients from southwest Sweden
- 1999
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Ingår i: Eur J Hum Genet. ; 7:7, s. 783-90
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Tidskriftsartikel (refereegranskat)abstract
- We have performed a pair-wise linkage study in the search for psoriasis susceptibility regions. A preliminary scan was performed on 20 families. In this set we obtained indications of linkage on chromosome 3q21. This region was further investigated using material from a total of 104 families (set 1B) resulting in a non-parametric linkage (NPL) of 1.77. The material was stratified in families whose parental origin is in southwest Sweden (set 1C). A maximum NPL value of 2.77 was obtained in this group. A transmission disequilibrium test (TDT) was performed on the stratified material (set 1C) and a significant P value of 0.005 was obtained, at marker D3S1269. The locus was confirmed with TDT in replicate material consisting of 148 families in which a single member was affected (P value 0.0007) at marker D3S1551. Thus, we have observed a significant P value using TDT in the vicinity of markers D3S1269/D3S1551, suggesting a novel psoriasis susceptibility region.
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| 7. |
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| 8. |
- Samuelsson, Lena, 1962, et al.
(författare)
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A genome-wide search for genes predisposing to familial psoriasis by using a stratification approach
- 1999
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Ingår i: Hum Genet. - 0340-6717 .- 0340-6717. ; 105:6, s. 523-9
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Tidskriftsartikel (refereegranskat)abstract
- We have performed a genome scan, using markers spaced by 10 cM, in the search for psoriasis-susceptibility loci. The family material of 134 affected sibling pairs was ascertained on the basis of a population genetic study in which 65% of the probands had two healthy parents. Genotyping results were analyzed for non-random excessive allele-sharing between sib pairs by using GENEHUNTER ver 1.1. A stratification approach was applied to increase the homogeneity of the material by means of an operational definition of joint complaints among affected individuals. Significant linkage to the human leukocyte antigen region on chromosome 6p in a cohort including 42 families without joint complaints (nonparametric linkage score of 2.83, P=0.002) strongly supported the validity of this operational definition as it replicated results from an earlier linkage report with similar stratification criteria. New candidate regions on chromosomes 3 and 15 were identified. The highest non-parametric linkage values in this study, 2.96 (P=0.0017) and 2.89 (P=0.0020), were reached on chromosome 15 in a subgroup with joint complaints and on chromosome 3 in a subgroup without joint complaints. In addition, confirmation of previously reported loci was established on chromosomes 4q, 6p, and 17q. This study indicates that distinct disease loci might be involved in psoriasis etiology for various phenotypes.
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| 9. |
- Swanbeck, Gunnar, 1934, et al.
(författare)
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Age at onset and different types of psoriasis
- 1995
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Ingår i: Br J Dermatol. ; 133:5, s. 768-73
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Tidskriftsartikel (refereegranskat)abstract
- The age at onset of psoriasis has been analysed for 11,366 psoriasis patients. The age at onset for siblings of probands has been analysed for 805 probands having one affected sibling and for 179 probands having two affected siblings. The age at onset curve for all probands shows a dominating maximum at about puberty but also indications for two more maxima at about 30 and 50 years of age, respectively. A more relevant picture of the risk of getting psoriasis at different ages is obtained if the onset for old people having psoriasis is investigated. The three maxima come out more clearly in this case, and the puberty maximum is not so dominating. For the families with one proband and two affected siblings there is a statistically significant correlation (P < 0.001) between the age at onset of the proband and of the siblings, and also between the siblings. The correlation coefficient is between 0.30 and 0.45. For the probands with one affected sibling, the ages at onset of the siblings mainly fall in the same range as those of the probands. These data indicate three groups of patients with respect to age at onset. However, the overlap between the different groups is considerable. The data presented are compatible with three, possibly genetically different, variants of psoriasis vulgaris. By studying the occurrence of psoriasis among parents of the probands, the gene frequency can be estimated assuming a recessive mode of inheritance. It then turns out that the gene frequency of the group with the earliest age at onset has a gene frequency of about 0.25, the next earliest, 0.18, and the latest, 0.14.
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| 10. |
- Swanbeck, Gunnar, 1934, et al.
(författare)
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Genetic counselling in psoriasis: empirical data on psoriasis among first-degree relatives of 3095 psoriatic probands
- 1997
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Ingår i: Br J Dermatol. ; 137:6, s. 939-42
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Tidskriftsartikel (refereegranskat)abstract
- The risk of getting psoriasis dependent on the occurrence of psoriasis in the family has been determined empirically. Altogether 3717 families with one or both parents who had psoriasis have been analysed with regard to the number of children with or without psoriasis. The lifetime risk of getting psoriasis if no parent, one parent or both parents have psoriasis is 0.04, 0.28 and 0.65, respectively. If there is already one affected child in the family, the corresponding risks are 0.24, 0.51 and 0.83, respectively. The risk of getting psoriasis before the age of 32 years is dependent on the age-of-onset of psoriasis in one affected parent.
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