Browsing by Subject "Mosaicism"

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  • Hydén-Granskog, Christel; Anttonen, Anna-Kaisa; Tiitinen, Aila (2018)
  • Alhopuro, Pia; Vainionpää, Reetta; Anttonen, Anna-Kaisa; Aittomäki, Kristiina; Nevanlinna, Heli; Pöyhönen, Minna (2020)
    Germline mutations in theBRCA1andBRCA2genes cause hereditary breast and ovarian cancer syndrome (HBOC). Mutations in these genes are usually inherited, and reports ofde novo BRCA1/2mutations are rare. To date, only one patient with low-levelBRCA1mutation mosaicism has been published. We report on a breast cancer patient with constitutional somatic mosaicism of aBRCA2mutation.BRCA2mutation c.9294C>G, p.(Tyr3098Ter) was detected in 20% of reads in DNA extracted from peripheral blood using next-generation sequencing (NGS). TheBRCA2mutation was subsequently observed at similar levels in normal breast tissue, adipose tissue, normal right fallopian tube tissue and ovaries of the patient, suggesting that this mutation occurred early in embryonic development. This is the first case to report constitutional mosaicism for aBRCA2mutation and shows thatBRCA2mosaicism can underlie early-onset breast cancer. NGS forBRCA1/2should be considered for patients whose tumors harbor aBRCA1/2mutation and for individuals suggestive of genetic predisposition but without a family history of HBO.
  • D'Amico, Adele; Fattori, Fabiana; Tasca, Giorgio; Petrini, Stefania; Gualandi, Francesca; Bruselles, Alessandro; D'Oria, Valentina; Verardo, Margherita; Carrozzo, Rosalba; Niceta, Marcello; Udd, Bjarne; Ferlini, Alessandra; Tartaglia, Marco; Bertini, Enrico (2017)
    Background: Collagen VI-related disorders (COL6-RD) are a group of heterogenous muscular diseases due to mutations in the COL6A1, COL6A2 and COL6A3 genes, encoding for collagen VI, a critical component of the extracellular matrix. Ullrich congenital muscle disorder and Bethlem myopathy represent the ends of a clinical spectrum that includes intermediate phenotypes of variable severity. UCMD are caused by recessive loss of function mutations or de-novo dominant-negative mutations. The intermediate phenotype and BM are more commonly caused by dominantly acting mutations, and less commonly by recessive mutations. Recently parental mosaicism for dominant mutations in COL6 have been reported in four COL6-RD families and germinal mosaicism has been also identified in a family with recurrence of UCMD in two half-sibs. Methods and results: Here we report three unrelated patients affected by a COL6-RD who carried de novo mosaic mutations in COL6A genes. These mutations, missed by Sanger sequencing, were identified by next generation sequencing. Conclusions: This report highlights the importance of a complete diagnostic workup when clinical and histological finding are consistent with a COL6-RD and strengthen the impression that mosaicisms are underestimated events underlying COL6-RD. (C) 2017 The Authors. Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.