| 1. |
- Bartik, Zsuzsa, et al.
(författare)
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A genome-wide scan to locate regions associated with familial vesicoureteral reflux
- 2022
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Ingår i: Experimental and Therapeutic Medicine. - : Spandidos Publications. - 1792-0981 .- 1792-1015. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Vesicoureteral reflux (VUR) is a congenital malformation carrying a high risk of recurrent urinary tract infections (UTI) and, at worst, chronic renal failure. Familial clustering implies a genetic etiology, but studies during the past few decades have demonstrated a causal gene variant in <10% of patients with VUR. The aim of the present study was to search for fully or partially shared ancestral haplotypes in 14 families from south-western Sweden with at least three affected members. High-density single nucleotide polymorphism microarray was used for genotyping prior to analysis with a compatibility matching method developed in-house, and the analysis of copy number variations (CNV). No single unique haplotype was revealed to be shared by the families, thereby excluding a common ancestry and founder mutations as a probable cause of VUR. After evaluation of haplotypes shared by subsets of families, a haplotype shared by nine families was found to be of particular interest. This haplotype, located at chromosomal region 4q21.21, harbours two tentative candidate genes (bone morphogenetic protein 3 and fibroblast growth factor 5), both expressed in metanephros and with known functions during nephrogenesis. As to CNV, only one family had a specific CNV shared by all affected members. This was a focal deletion at 5q31.1 including follistatin-like 4, a gene without a previous known connection to VUR. These data demonstrated the genetic heterogeneity of VUR and indicated that an interaction of environmental and genetic factors, including non-coding and epigenetic regulators, all contribute to the complexity of VUR.
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| 2. |
- Bartik, Zsuzsa, et al.
(författare)
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Hereditary Vesicoureteral Reflux: A Study of 66 Families
- 2015
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Ingår i: Open Journal of Pediatrics. - : Scientific Research Publishing, Inc.. - 2160-8741 .- 2160-8776. ; 2015:5, s. 304-313
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We studied the inheritance pattern, clinical features and outcome in children with vesicoureteral reflux (VUR). Characteristics of known familial VUR cases were also compared with those of sporadic VUR. Material and Methods: 726 patients were treated for VUR between 1990-2004. The families were contacted by letter inquiring if other members of the family were affected. The phenotype of all cases (familial and non-familial) was characterized in terms of presenting symptoms, reflux grade, recurrent urinary tract infections, kidney damage, and the natural course of reflux. Results: The response rate was 79%. A total of 99 individuals (22%) reported relatives with VUR. Since some of the 99 index cases belonged to the same family, the total number of families was ultimately 66. The distribution of relatives with VUR was: 38 siblings, 20 parents (15 mothers), 19 cousins, 15 aunts/uncles and 12 grandparents. The phenotype of VUR did not differ between familial and non-familial cases. However, VUR among relatives was of milder grade than index and sporadic cases. Conclusions: The proportion of hereditary reflux in our material was lower than in other studies (22%). We found a strong overrepresentation of maternal transmission of reflux. Severity of the disease did not differ between familial and non-familial VUR.
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| 3. |
- Bartik, Zsuzsa, et al.
(författare)
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Whole exome sequencing identifies KIF26B, LIFR and LAMC1 mutations in familial vesicoureteral reflux
- 2022
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Vesicoureteral reflux (VUR) is a common urological problem in children and its hereditary nature is well recognised. However, despite decades of research, the aetiological factors are poorly understood and the genetic background has been elucidated in only a minority of cases. To explore the molecular aetiology of primary hereditary VUR, we performed wholeexome sequencing in 13 large families with at least three affected cases. A large proportion of our study cohort had congenital renal hypodysplasia in addition to VUR. This highthroughput screening revealed 23 deleterious heterozygous variants in 19 candidate genes associated with VUR or nephrogenesis. Sanger sequencing and segregation analysis in the entire families confirmed the following findings in three genes in three families: frameshift LAMC1 variant and missense variants of KIF26B and LIFR genes. Rare variants were also found in SALL1, ROBO2 and UPK3A. These gene variants were present in individual cases but did not segregate with disease in families. In all, we demonstrate a likely causal gene variant in 23% of the families. Whole-exome sequencing technology in combination with a segregation study of the whole family is a useful tool when it comes to understanding pathogenesis and improving molecular diagnostics of this highly heterogeneous malformation.
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| 4. |
- Evertsson, Sofia, 1972-, et al.
(författare)
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Apoptosis in relation to proliferating cell nuclear antigen and Dukes' stage in colorectal adenocarcinoma
- 1999
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 15:1, s. 53-58
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer is a disease that is associated with default in the balance of apoptotic regulation. In the present study apoptosis was examined in 158 colorectal adenocarcinomas using the terminal deoxynucleotidyl transferase mediated digoxigenin nick end labeling (TUNEL) method. The median apoptotic index (AI) was 0.95% (range 0-6. 68%). Eighty-two tumours exhibited AI 0.95%. We revealed a positive correlation between apoptosis and proliferation determined as the expression of proliferating cell nuclear antigen (PCNA, p=0.002). The frequency of apoptosis increased from Dukes' stage A, B, C to D (p=0.01). No correlations were found between apoptosis and the patients' sex, age, tumour location, growth pattern, differentiation, prognosis, bcl-2, p53 or K-ras. Our findings suggest that we should further investigate the relationship between apoptosis and cellular proliferative activity in colorectal cancer to evaluate whether this might provide additional information in the selection of patients for effective adjuvant therapy.
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| 5. |
- Hössjer, Therese, et al.
(författare)
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Complication rate after gastrostomy placement in children can be reduced by simple surgical steps
- 2023
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Ingår i: Acta Pædiatrica. - : John Wiley & Sons. - 1651-2227 .- 0803-5253. ; 112:7, s. 1597-1604
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To evaluate if the incidence of postoperative complications after gastrostomy placement is correlated to perioperative parameters or patient characteristics.METHODS: In this prospective observational study, children <18 years of age planned to receive a gastrostomy at partaking clinics between 2014 and 2019 were invited. Pre-, peri- and postoperative variables were collected and followed up 3 months postoperatively.RESULTS: Five hundred and eighty-two patients were included (median age: 26 months, median weight: 10.8 kg), mainly laparoscopic (52.0%) and push-PEG (30.2%) technique used. The incidence of complications was lower in the group of patients receiving a gastrostomy tube that was 2 mm longer than the gastrostomy canal (p < 0.001-0.025), and a thickness of 12 Fr (p < 0.001-0.009). These findings were confirmed by multivariate analysis also including operative technique, age and weight. Patients with oncological disease had significantly higher incidence of pain and infection but the lowest incidence of granulomas (p < 0.001-0.01).CONCLUSION: This study indicates that a 12 Fr gastrostomy tube that is 2 mm longer than the gastrostomy canal is correlated with the lowest incidence of postoperative complications the first 3 months after surgery. Oncological patients had the lowest incidence of granulomas which probably is related to chemotherapy.
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| 6. |
- Sun, Xiao-Feng, 1959-, et al.
(författare)
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Bcl-2 expression is a prognostic factor in the subgroups of patients with colorectal cancer.
- 2003
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 23:5, s. 1439-1443
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Tidskriftsartikel (refereegranskat)abstract
- The prognostic significance of Bcl-2 expression in colorectal cancer has been intensively studied, however, the results were controversial in the whole group of colorectal cancer patients. We proposed that one of the main reasons for such controversial results may be that Bcl-2 played variable roles in the subgroup of patients. We, therefore, investigated the prognostic importance of Bcl-2 expression by using immunohistochemistry in the various subgroups of 147 patients with colorectal cancer. Among these tumours, 85 (58%) expressed Bcl-2 protein and 62 (42%) were negative. Bcl-2 expression was positively related to DCC expression (p=0.0002). Survival analyses in the subgroups of the patients showed that lack of Bcl-2 expression was related to a worse prognosis in the male patients (p=0.02) but not in female patients (p=0.53), in the patients with DNA diploid tumours (p=0.005) not in the patients with non-diploid tumours (p=0.46), and in the patients with ras negative tumours (p=0.01) not in the patients with ras positive tumours (p=0.25). Bcl-2 expression was not related to prognosis in the total group of the patients (p=0.20). In conclusion, Bcl-2 protein may play variable prognostic roles in the subgroups of the patients with colorectal cancer. Analysis of Bcl-2 expression in the tumour may be of value in predicting prognosis and therapeutic response.
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| 7. |
- Zu, Shulu, et al.
(författare)
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Mutations in the ROBO2 and SLIT2 genes are rare causes of familial vesico-ureteral reflux.
- 2009
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Ingår i: Pediatric nephrology (Berlin, Germany). - : Springer Science and Business Media LLC. - 1432-198X .- 0931-041X. ; 24:8, s. 1501-8
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Tidskriftsartikel (refereegranskat)abstract
- Familial clustering of vesico-ureteral reflux (VUR) suggests that genetic factors play an important role in the pathogenesis of this condition. The SLIT2 protein and its receptor, ROBO2, have key functions in the formation of the ureteric bud. Two recent studies have found that ROBO2 gene missense mutations are associated with VUR. In the study reported here, we investigated the genetic contribution of the SLIT2 and ROBO2 genes in non-syndromic familial VUR by mutation screening of 54 unrelated patients with primary VUR. Direct sequencing of all 26 exons and the exon-intron boundaries revealed six ROBO2 gene variants, two of which were new. Direct sequencing of all 37 exons and the exon-intron boundaries identified 20 SLIT2 gene variants, two of which were new. One variant, c.4253C > T, which was found in two families, leads to an amino acid substitution in a relatively well-conserved amino acid, p.Ala1418Val, which was predicted to cause an altered secondary structure but to have little impact on the three-dimensional structure. This missense variant did not segregate with VUR in these two families and was not found in 96 control subjects. We conclude that gene variants in ROBO2 and SLIT2 are rare causes of VUR in humans. Our results provide further evidence for the genetic heterogeneity of this disorder.
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