| 1. |
- Andersson, Ulrika, et al.
(author)
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Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer
- 2014
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In: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 16:10, s. 1333-1340
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Journal article (peer-reviewed)abstract
- Background: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. Methods: Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer. The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma. Results: We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer. Conclusions: Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes.
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| 2. |
- Olsson, Malin, et al.
(author)
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A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers
- 2010
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In: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 11, s. 130-
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Journal article (peer-reviewed)abstract
- Our results are the first to show the presence of a 3'UTR polymorphism on the V30M haplotype in Swedish carriers, which can serve as a miRNA binding site potentially leading to down-regulated expression from the mutated TTR allele. This finding may be related to the low penetrance and high age at onset of the disease observed in the Swedish patient population.
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| 3. |
- Olsson, Malin, 1972-, et al.
(author)
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Frequency of the transthyretin Val30Met mutation in the northern Swedish population
- 2014
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In: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 21:1, s. 18-20
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Journal article (other academic/artistic)abstract
- By genotyping a large number of samples from the Northern Sweden Health and Disease Study cohort, a carrier frequency could be determined for the Skelleftea and Lycksele populations. A previous study of the amyloidogenic transthyretin mutation TTRV30M in Northern Sweden's endemic area has shown a large variation in carrier frequency and penetrance of the trait within the area. However, the estimations have been based on a small sample size within the different regions in the area and therefore, the wide variation in TTRV30M carrier frequency observed between the Lycksele and Skelleftea populations are uncertain. Based on a total of 3460 samples, the estimated overall carrier frequency in the two regions was 1.82% with a carrier frequency in the Skelleftea and Lycksele population of 1.63% and 2.02%, respectively. Thus, the previously reported extremely high frequency in the Lycksele region compared to that of the Skelleftea region could not be substantiated. However, it does not change the previous finding of a surprisingly higher carrier frequency in the population from endemic area of Northern Sweden compared to that reported from endemic areas in Portugal.
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| 4. |
- Stattin, Eva-Lena, et al.
(author)
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Founder mutations characterise the mutation panorama in 200 Swedish index cases referred for Long QT syndrome genetic testing
- 2012
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In: BMC Cardiovascular Disorders. - : BioMed Central. - 1471-2261 .- 1471-2261. ; 12, s. 95-
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Journal article (peer-reviewed)abstract
- Background: Long QT syndrome (LQTS) is an inherited arrhythmic disorder characterised by prolongation of the QT interval on ECG, presence of syncope and sudden death. The symptoms in LQTS patients are highly variable, and genotype influences the clinical course. This study aims to report the spectrum of LQTS mutations in a Swedish cohort.Methods: Between March 2006 and October 2009, two hundred, unrelated index cases were referred to the Department of Clinical Genetics, Umea University Hospital, Sweden, for LQTS genetic testing. We scanned five of the LQTS-susceptibility genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2) for mutations by DHPLC and/or sequencing. We applied MLPA to detect large deletions or duplications in the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes. Furthermore, the gene RYR2 was screened in 36 selected LQTS genotype-negative patients to detect cases with the clinically overlapping disease catecholaminergic polymorphic ventricular tachycardia (CPVT).Results: In total, a disease-causing mutation was identified in 103 of the 200 (52%) index cases. Of these, altered exon copy numbers in the KCNH2 gene accounted for 2% of the mutations, whereas a RYR2 mutation accounted for 3% of the mutations. The genotype-positive cases stemmed from 64 distinct mutations, of which 28% were novel to this cohort. The majority of the distinct mutations were found in a single case (80%), whereas 20% of the mutations were observed more than once. Two founder mutations, KCNQ1 p.Y111C and KCNQ1 p.R518*, accounted for 25% of the genotype-positive index cases. Genetic cascade screening of 481 relatives to the 103 index cases with an identified mutation revealed 41% mutation carriers who were at risk of cardiac events such as syncope or sudden unexpected death.Conclusion: In this cohort of Swedish index cases with suspected LQTS, a disease-causing mutation was identified in 52% of the referred patients. Copy number variations explained 2% of the mutations and 3 of 36 selected cases (8%) harboured a mutation in the RYR2 gene. The mutation panorama is characterised by founder mutations (25%), even so, this cohort increases the amount of known LQTS-associated mutations, as approximately one-third (28%) of the detected mutations were unique.
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