Frank S, Gabassi E, Käseberg S, Bertin M, Zografidou L, Pfeiffer D, Brennenstuhl H, Falk S, Karow M, Schweiger S (2024)
Publication Type: Journal article
Publication year: 2024
Book Volume: 7
Journal Issue: 4
The X-linked form of Opitz BBB/G syndrome (OS) is a monogenic disorder in which symptoms are established early during embryonic development. OS is caused by pathogenic variants in the X-linked gene MID1 Disease-associated variants are distributed across the entire gene locus, except for the N-terminal really interesting new gene (RING) domain that encompasses the E3 ubiquitin ligase activity. By using genome-edited human induced pluripotent stem cell lines, we here show that absence of isoforms containing the RING domain of MID1 causes severe patterning defects in human brain organoids. We observed a prominent neurogenic deficit with a reduction in neural tissue and a concomitant increase in choroid plexus-like structures. Transcriptome analyses revealed a deregulation of patterning pathways very early on, even preceding neural induction. Notably, the observed phenotypes starkly contrast with those observed in MID1 full-knockout organoids, indicating the presence of a distinct mechanism that underlies the patterning defects. The severity and early onset of these phenotypes could potentially account for the absence of patients carrying pathogenic variants in exon 1 of the MID1 gene coding for the N-terminal RING domain.
APA:
Frank, S., Gabassi, E., Käseberg, S., Bertin, M., Zografidou, L., Pfeiffer, D.,... Schweiger, S. (2024). Absence of the RING domain in MID1 results in patterning defects in the developing human brain. Life Science Alliance, 7(4). https://doi.org/10.26508/lsa.202302288
MLA:
Frank, Sarah, et al. "Absence of the RING domain in MID1 results in patterning defects in the developing human brain." Life Science Alliance 7.4 (2024).
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