| 1. |
- Isaksson, Magnus, et al.
(författare)
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MLGA--a rapid and cost-efficient assay for gene copy-number analysis
- 2007
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 35:17, s. e115-
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Tidskriftsartikel (refereegranskat)abstract
- Structural variation is an important cause of genetic variation. Whole genome analysis techniques can efficiently identify copy-number variable regions but there is a need for targeted methods, to verify and accurately size variable regions, and to diagnose large sample cohorts. We have developed a technique based on multiplex amplification of size-coded selectively circularized genomic fragments, which is robust, cheaper and more rapid than current multiplex targeted copy-number assays.
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| 2. |
- Nyström, Anna-Maja, et al.
(författare)
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A severe form of Noonan syndrome and autosomal dominant café-au-lait spots : evidence for different genetic origins
- 2009
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 98:4, s. 693-698
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The clinical overlap among Noonan syndrome (NS), cardio-facio-cutaneous (CFC), LEOPARD and Costello syndromes as well as Neurofibromatosis type 1 is extensive, which complicates the process of diagnosis. Further genotype–phenotype correlations are required to facilitate future diagnosis of these patients. Therefore, investigations of the genetic cause of a severe phenotype in a patient with NS and the presence of multiple café-au-lait spots (CAL) spots in the patient and four members of the family were performed. Methods: Mutation analyses of candidate genes, PTPN11, NF1, SPRED1 and SPRED2, associated with these syndromes, were conducted using DNA sequencing. Results: A previously identified de novo mutation, PTPN11 F285L and an inherited NF1 R1809C substitution in the index patient were found. However, neither PTPN11 F285L, NF1 R1809C, SPRED1 nor SPRED2 segregated with CAL spots in the family. The results indicate that the familial CAL spots trait in this family is caused by a mutation in another gene, distinct from previous genes associated with CAL spots in these syndromes. Conclusion: We suggest that the atypical severe symptoms in the index patient may be caused by an additive effect on the F285L mutation in PTPN11 by another mutation, for example the NF1 R1809C or alternatively, the not yet identified gene mutation associated with CAL spots in this family.
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| 3. |
- Schoumans, Jacqueline, et al.
(författare)
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Comprehensive mutational analysis of a cohort of Swedish Cornelia de Lange syndrome patients
- 2007
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 15:2, s. 143-149
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Tidskriftsartikel (refereegranskat)abstract
- Cornelia de Lange syndrome (CdLS; OMIM 122470) is a rare multiple congenital anomaly/mental retardation syndrome characterized by distinctive dysmorphic facial features, severe growth and developmental delay and abnormalities of the upper limbs. About 50% of CdLS patients have been found to have heterozygous mutations in the NIPBL gene and a few cases were recently found to be caused by mutations in the X-linked SMC1L1 gene. We performed a mutation screening of all NIPBL coding exons by direct sequencing in 11 patients (nine sporadic and two familial cases) diagnosed with CdLS in Sweden and detected mutations in seven of the cases. All were de novo, and six of the mutations have not been previously described. Four patients without identifiable NIPBL mutations were subsequently subjected to multiplex ligation-dependent probe amplification analysis to exclude whole exon deletions/duplications of NIPBL. In addition, mutation analysis of the 5' untranslated region (5' UTR) of NIPBL was performed. Tiling resolution array comparative genomic hybridization analysis was carried out on these four patients to detect cryptic chromosome imbalances and in addition the boys were screened for SMC1L1 mutations. We found a de novo 9p duplication with a size of 0.6 Mb in one of the patients with a CdLS-like phenotype but no mutations were detected in SMC1L1. So far, two genes (NIPBL and SMC1L1) have been identified causing CdLS or CdLS-like phenotypes. However, in a considerable proportion of individuals demonstrating the CdLS phenotype, mutations in any of these two genes are not found and other potential loci harboring additional CdLS-causing genes should be considered.
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| 4. |
- Thuresson, Ann-Charlotte, et al.
(författare)
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Whole-genome array-CGH for detection of submicroscopic chromosomal imbalances in children with mental retardation
- 2007
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Ingår i: Cytogenetic and Genome Research. - : S. Karger AG. - 1424-8581 .- 1424-859X. ; 118:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Chromosomal imbalances are the major cause of mental retardation (MR). Many of these imbalances are caused by submicroscopic deletions or duplications not detected by conventional cytogenetic methods. Microarray-based comparative genomic hybridization (array-CGH) is considered to be superior for the investigation of chromosomal aberrations in children with MR, and has been demonstrated to improve the diagnostic detection rate of these small chromosomal abnormalities. In this study we used 1 Mb genome-wide array-CGH to screen 48 children with MR and congenital malformations for submicroscopic chromosomal imbalances, where the underlying cause was unknown. All children were clinically investigated and subtelomere FISH analysis had been performed in all cases. Suspected microdeletion syndromes such as deletion 22q11.2, Williams-Beuren and Angelman syndromes were excluded before array-CGH analysis was performed. We identified de novo interstitial chromosomal imbalances in two patients (4%), and an interstitial deletion inherited from an affected mother in one patient (2%). In another two of the children (4%), suspected imbalances were detected but were also found in one of the non-affected parents. The yield of identified de novo alterations detected in this study is somewhat less than previously described, and might reflect the importance of which selection criterion of patients to be used before array-CGH analysis is performed. However, array-CGH proved to be a high-quality and reliable tool for genome-wide screening of MR patients of unknown etiology.
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| 5. |
- Thuresson, Marie, et al.
(författare)
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Factors that influence the use of ambulance in acute coronary syndrome.
- 2008
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Ingår i: American heart journal. - Amsterdam : Elsevier BV. - 1097-6744 .- 0002-8703. ; 156:1, s. 170-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: National guidelines recommend activation of the emergency medical service by patients who have symptoms of acute coronary syndrome (ACS). In spite of this, only 50% to 60% of persons with myocardial infarction initiate care by using the emergency medical service. The aim of this study was to define factors influencing the use of ambulance in ACS. METHODS: The method used in this study was a national survey comprising intensive cardiac care units at 11 hospitals in Sweden; 1,939 patients with diagnosed ACS and symptom onset outside the hospital completed a questionnaire a few days after admission. RESULTS: Half of the patients went to the hospital by ambulance. Factors associated with ambulance use were knowledge of the importance of quickly seeking medical care and calling for an ambulance when having chest pain (odds ratio [OR] 3.61, 95% CI 2.43-5.45), abrupt onset of pain reaching maximum intensity within minutes (OR 2.08, 1.62-2.69), nausea or cold sweat (OR 2.02, 1.54-2.65), vertigo or near syncope (OR 1.63, 1.21-2.20), ST-elevation ACS (OR 1.58, 1.21-2.06), increasing age (per year) (OR 1.03, 1.02-1.04), previous history of heart failure (OR 2.48, 1.47-4.26), and distance to the hospital of >5 km (OR 2.0, 1.55-2.59). Those who did not call for an ambulance thought self-transport would be faster or did not believe they were sick enough. CONCLUSIONS: Symptoms, patient characteristics, ACS characteristics, and perceptions and knowledge were all associated with ambulance use in ACS. The fact that knowledge increases ambulance use and the need for behavioral change pose a challenge for health-care professionals.
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| 6. |
- Thuresson, Marie, et al.
(författare)
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Symptoms and type of symptom onset in acute coronary syndrome in relation to ST elevation, sex, age, and a history of diabetes
- 2005
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Ingår i: Am Heart J. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 150:2, s. 234-42
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Various efforts to reduce patient delay in acute coronary syndrome (ACS) have had limited success. One reason might be a misinterpretation of the symptoms of ACS. The aim of this study was therefore to explore the characteristics and severity of symptoms among patients with an ACS in overall terms and in relation to the type of ACS, sex, age, and diabetes. METHODS: A total of 1939 patients at 11 hospitals in Sweden answered a questionnaire containing questions relating to the localization and intensity of symptoms, the presence of associated symptoms, the characteristics and experience of pain/symptoms, and the type of symptom onset. RESULTS: Patients with ST elevation differed from those without by more frequently having associated symptoms. They had higher pain/discomfort intensity and more frequently had pain with abrupt onset reaching maximum intensity within minutes. However, this type of symptom onset was only seen in less than half the patients with ST elevation and only 1 in 5 fulfilled all the criteria usually associated with a severe heart attack. Women differed from men in a few respects. They more frequently reported pain/discomfort in the neck or jaw and back, vomiting, and scored their pain/discomfort slightly higher than men. Differences between age groups were minor and there was no difference between patients with and without diabetes. CONCLUSIONS: The most striking finding was the low proportion of patients with the type of symptoms that are commonly associated with ACS. This is important for the planning of educational campaigns/programs to reduce patient delay.
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| 7. |
- Thuresson, Marie, et al.
(författare)
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Thoughts, actions, and factors associated with prehospital delay in patients with acute coronary syndrome.
- 2007
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Ingår i: Heart & Lung. - Amsterdam : Elsevier BV. - 0147-9563 .- 1527-3288. ; 36:6, s. 398-409
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Tidskriftsartikel (refereegranskat)abstract
- Objective The objective was to study patients’ interpretations, thoughts, and actions after symptom onset in acute coronary syndrome (ACS) in total and in relation to gender, age, history of coronary artery disease, type of syndrome, and residential area and its influence on prehospital delay. Setting We performed a national survey comprising intensive cardiac care units at 11 hospitals in Sweden. Method A total of 1939 patients with diagnosed ACS and symptom onset outside hospital completed a questionnaire containing standardized questions within 3 days after admission. Results Three-quarters of the patients interpreted their symptoms as cardiac in origin, and the most common reason was that they knew someone who had had an acute myocardial infarction. The majority contacted a family member, whereas only 3% directly called for an ambulance. Interpreting the symptoms as cardiac in origin and severe pain were major reasons for deciding to seek medical care. Approaching someone after symptom onset and the belief that the symptoms were cardiac in origin were factors associated with a shorter prehospital delay, whereas taking medication to relieve pain resulted in the opposite. The reaction pattern was influenced by gender, age, a history of coronary artery disease, and the type of ACS, but to a lesser extent by residential area. Conclusions Interpreting symptoms as cardiac in origin and approaching someone after symptom onset were major reasons for a shorter prehospital delay in ACS.
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