Correlation Engine 2.0
Clear Search sequence regions


  • adult (1)
  • alleles (3)
  • child (1)
  • children (1)
  • female (1)
  • gene (1)
  • GRIN2A (3)
  • humans (1)
  • impairment (1)
  • methyl (3)
  • mother (5)
  • proband (1)
  • receptors d (2)
  • receptors d (1)
  • sister (2)
  • Sizes of these terms reflect their relevance to your search.

    We aim to describe double gonosomal mosaicism in the GRIN2A gene in a mother who passed on two different pathogenic variants at the same nucleotide to her two affected children. We studied a boy with epilepsy and intellectual disability, along with his sister and mother who exhibited language impairment and learning difficulties without epilepsy. We identified in the proband a splice-site variant in GRIN2A (c.1008-1G>A) inherited from his mother. Subsequent testing of his sister revealed a different change at the same nucleotide c.1008-1G>T, which was also present in the mother's DNA at 3.9% allele frequency. The co-occurrence of two mutational events at the same nucleotide is extremely rare. Since a chance occurrence is unlikely, we hypothesise that a base mismatch may introduce instability triggering a second event. In this family, the mother carries three alleles, of which one is at very low frequency. This complex genetic landscape poses diagnostic challenges since low-level mosaicism may escape detection via conventional methods. Applying specific technology becomes crucial, as double mosaicism might prove to be more prevalent than anticipated severely impacting diagnostic accuracy and genetic counselling. © Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.

    Citation

    Valentina Cetica, Mara Cavallin, Maria Luisa Ricci, Claudia Mandorlini, Emanuele Bartolini, Elena Parrini, Renzo Guerrini. Double gonosomal mosaicism as an unusual hereditary mechanism in familial GRIN2A-related disorder. Journal of medical genetics. 2024 Sep 24;61(10):999-1002

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 39084904

    View Full Text