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- Kuusisto, Kirsi M., et al.
(författare)
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Copy Number Variation Analysis in Familial BRCA1/2-Negative Finnish Breast and Ovarian Cancer
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inherited factors predisposing individuals to breast and ovarian cancer are largely unidentified in a majority of families with hereditary breast and ovarian cancer (HBOC). We aimed to identify germline copy number variations (CNVs) contributing to HBOC susceptibility in the Finnish population. Methods: A cohort of 84 HBOC individuals (negative for BRCA1/2-founder mutations and pre-screened for the most common breast cancer genes) and 36 healthy controls were analysed with a genome-wide SNP array. CNV-affecting genes were further studied by Gene Ontology term enrichment, pathway analyses, and database searches to reveal genes with potential for breast and ovarian cancer predisposition. CNVs that were considered to be important were validated and genotyped in 20 additional HBOC individuals (6 CNVs) and in additional healthy controls (5 CNVs) by qPCR. Results: An intronic deletion in the EPHA3 receptor tyrosine kinase was enriched in HBOC individuals (12 of 101, 11.9%) compared with controls (27 of 432, 6.3%) (OR = 1.96; P = 0.055). EPHA3 was identified in several enriched molecular functions including receptor activity. Both a novel intronic deletion in the CSMD1 tumor suppressor gene and a homozygous intergenic deletion at 5q15 were identified in 1 of 101 (1.0%) HBOC individuals but were very rare (1 of 436, 0.2% and 1 of 899, 0.1%, respectively) in healthy controls suggesting that these variants confer disease susceptibility. Conclusion: This study reveals new information regarding the germline CNVs that likely contribute to HBOC susceptibility in Finland. This information may be used to facilitate the genetic counselling of HBOC individuals but the preliminary results warrant additional studies of a larger study group.
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| 2. |
- Raivio, Virpi Elisa, et al.
(författare)
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A novel transthyretin Lys70Glu (p.Lys90Glu) mutation presenting with vitreous amyloidosis and carpal tunnel syndrome
- 2016
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Ingår i: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 23:1, s. 46-50
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We describe a novel TTR mutation with vitreous opacities and carpal tunnel syndrome. Materials and methods: A 78 year-old woman with vitreous opacities, her daughter with dry eye syndrome, and brother with carpal tunnel syndrome were tested for a mutation in the TTR gene. The vitreous opacities were removed and stained with Congo red and immunohistochemistry against wild type TTR. Skin and gut biopsies and specimens of soft tissue were examined histopathologically. Leukocyte DNA from the proband was analysed by direct sequencing of exons 1 to 4 of the TTR gene and DNA from her daughter and brother using segregation analysis. Results: A point mutation c.268 A>C, in the TTR gene, leading to a missense mutation p.Lys90Glu was found in all subjects. The vitreous opacities were pearl string-like. Histopathology showed red to green birefringence in Congo red, typical to amyloid, and the specimens were immunoreactive with antibodies against TTR. Conclusion: We present a novel autosomally inherited Lys90Glu mutation in the TTR gene. This is the first reported FAP family with this mutation in Finland.
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