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- Henstrom, M., et al.
(författare)
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Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome
- 2018
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 67:2, s. 263-270
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Tidskriftsartikel (refereegranskat)abstract
- Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucraseisomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p. Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.
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- Magnusson, Gunilla, 1968, et al.
(författare)
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Evaluation of screening procedures for congenital cataracts.
- 2003
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 0803-5253 .- 1651-2227. ; 92:12, s. 1468-73
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To evaluate the efficacy of two different Swedish screening procedures for early detection of congenital cataracts in comparison with no screening. METHODS: Children born between January 1992 and December 1998 in Swedish regions with an established eye-screening routine procedure, diagnosed with congenital cataract, and operated on before 1 y of age, were included in a retrospective study. Age at referral and age at time of the operation were compared between regions using different screening procedures: screening in the maternity wards (Region 1), at the well-baby clinics (Region 2) and one region without any screening (Region 3). RESULTS: Seventy-two children were included in the study. Concerning early diagnosis and surgery, Region 1 differed significantly from Regions 2 and 3, which were more similar and were combined for further analysis. The difference in detected cases was greatest at 21 d of age (55% vs 18%; p < 0.001), but persisted even at 100 d of age (78% vs 64%; p < 0.02). Region 1 screening resulted in more and earlier cases detected than the other two regions (22 vs 15 per 100,000 births). In 72% of all cases, surgery was performed in response to referrals from either the maternity wards (36%), or the well-baby clinics (36%). However, half of the cases from the well-baby clinics were detected too late, i.e. at > 100 d. CONCLUSION: Eye screening in the maternity ward is preferable to well-baby clinic screening and to no screening at all, since it leads to early detection. Screening should also be performed routinely at well-baby clinics within the period when successful treatment is possible.
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- Andreasson, M, et al.
(författare)
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MCEE Mutations in an Adult Patient with Parkinson's Disease, Dementia, Stroke and Elevated Levels of Methylmalonic Acid
- 2019
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 20:11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Methylmalonic aciduria (MMA-uria) is seen in several inborn errors of metabolism (IEM) affecting intracellular cobalamin pathways. Methylmalonyl-CoA epimerase (MCE) is an enzyme involved in the mitochondrial cobalamin-dependent pathway generating succinyl-CoA. Homozygous mutations in the corresponding MCEE gene have been shown in children to cause MCE deficiency with isolated MMA-uria and a variable clinical phenotype. We describe a 78-year-old man with Parkinson’s disease, dementia and stroke in whom elevated serum levels of methylmalonic acid had been evident for many years. Metabolic work-up revealed intermittent MMA-uria and increased plasma levels of propionyl-carnitine not responsive to treatment with high-dose hydroxycobalamin. Whole genome sequencing was performed, with data analysis targeted towards genes known to cause IEM. Compound heterozygous mutations were identified in the MCEE gene, c.139C>T (p.Arg47X) and c.419delA (p.Lys140fs), of which the latter is novel. To our knowledge, this is the first report of an adult patient with MCEE mutations and MMA-uria, thus adding novel data to the possible phenotypical spectrum of MCE deficiency. Although clinical implications are uncertain, it can be speculated whether intermittent hyperammonemia during episodes of metabolic stress could have precipitated the patient’s ongoing neurodegeneration attributed to Parkinson’s disease.
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- Beijer, U, et al.
(författare)
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Mortality and causes of death among homeless women and men in Stockholm
- 2011
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 39:2, s. 121-127
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To study the mortality and causes of death among homeless men and women in relation to the risk indicators, previous treatment for alcohol and drug abuse, previous treatment for mental disorders and non-Swedish citizenship. Methods: The mortality was studied in a cohort comprising 1,757 men and 526 women compared with the general population and persons with inpatient treatment for alcohol- and drug-related disorders. The follow-up period was from 1995 to 1997 until the end of 2005. The causes of death were analyzed. Results: 421 deaths occurred during the follow-up period. The relative risk of death was 3.1, with no difference in mortality between homeless men and homeless women. Previous treatment for alcohol and drug abuse disorders was related to excess mortality and previous treatment for mental disease to lower mortality. Homeless people with inpatient treatment for alcohol or drug use disorders had no higher mortality than the general population in Stockholm with a similar history. There was a dominance of alcohol- and drug-related causes of death. Discussion: Compared with previous studies of homeless people in Stockholm the excess mortality among men found in this study is of the same magnitude. Mortality among women is lower. The mortality rate in homeless people with previous treatment for an alcohol and illicit drug use disorder did not differ from those treated for these disorders in the general population. Conclusions: The most important finding is that excess mortality among homeless men and women in Stockholm is entirely related to alcohol and drug abuse.
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