Professional Education

  • PhD, University of Chicago, Cancer Biology (2021)
  • Master of Science, University of Chicago, Translational Research (2016)
  • Bachelor of Art, Vanderbilt University, Molecular and Cellular Biology Economics (2013)

Stanford Advisors

Lab Affiliations

All Publications

  • RBL2 bi-allelic truncating variants cause severe motor and cognitive impairment without evidence for abnormalities in DNA methylation or telomeric function JOURNAL OF HUMAN GENETICS Samra, N., Toubiana, S., Yttervik, H., Tzur-Gilat, A., Morani, I., Itzkovich, C., Giladi, L., Abu Jabal, K., Cao, J. Z., Godley, L. A., Mory, A., Baris Feldman, H., Tveten, K., Selig, S., Weiss, K. 2021; 66 (11): 1101-1112


    RBL2/p130, a member of the retinoblastoma family of proteins, is a key regulator of cell division and propagates irreversible senescence. RBL2/p130 is also involved in neuronal differentiation and survival, and eliminating Rbl2 in certain mouse strains leads to embryonic lethality accompanied by an abnormal central nervous system (CNS) phenotype. Conflicting reports exist regarding a role of RBL2/p130 in transcriptional regulation of DNA methyltransferases (DNMTs), as well as the control of telomere length. Here we describe the phenotype of three patients carrying bi-allelic RBL2-truncating variants. All presented with infantile hypotonia, severe developmental delay and microcephaly. Malignancies were not reported in carriers or patients. Previous studies carried out on mice and human cultured cells, associated RBL2 loss to DNA methylation and telomere length dysregulation. Here, we investigated whether patient cells lacking RBL2 display related abnormalities. The study of primary patient fibroblasts did not detect abnormalities in expression of DNMTs. Furthermore, methylation levels of whole genome DNA, and specifically of pericentromeric repeats and subtelomeric regions, were unperturbed. RBL2-null fibroblasts show no evidence for abnormal elongation by telomeric recombination. Finally, gradual telomere shortening, and normal onset of senescence were observed following continuous culturing of RBL2-mutated fibroblasts. Thus, this study resolves uncertainties regarding a potential non-redundant role for RBL2 in DNA methylation and telomere length regulation, and indicates that loss of function variants in RBL2 cause a severe autosomal recessive neurodevelopmental disorder in humans.

    View details for DOI 10.1038/s10038-021-00931-z

    View details for Web of Science ID 000650066100001

    View details for PubMedID 33980986