Brain somatic mosaicism of sex chromosomes defines MOGHE

Cecchini E, Coras R, Katoch M, Kobow K, Hartlieb T, Bien C, Blümcke I, Hoffmann L (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 65

Pages Range: 50-51

Article Number: 1297

Issue: S1

DOI: 10.1111/epi.18151

Abstract

Purpose: Recent studies on sex chromosome-associated
epilepsies highlighted a connection with aberrant neural
development, e.g. in the Rett or Klinefelter syndromes.
Herein we propose that the new disease entity
termed “Mild malformation of cortical development with
OligodendroGlial Hyperplasia in Epilepsy” (MOGHE) is
also linked to altered sex chromosomes.
Method: We studied 35 individuals with MOGHE, including
20 males and 15 females (Table 1). 19 of 28 individuals
tested for the X-linked
SLC35A2 galactose transporter
gene in neurosurgically resected brain tissue, and demonstrating
histopathologic landmarks of oligodendroglial
hyperplasia, myelin loss and heterotopic neurons in the
white matter, carried a pathogenic variant (68%).
15281167, 2024, S1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/epi.18151 by Friedrich-Alexander Universität Of Erlangen-Nürnberg, Wiley Online Library on [10/12/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
ABSTRACT | 51
Results: Interestingly, Copy Number Variation (CNV)
plots derived from DNA methylation analysis revealed
significant gains of the Y chromosome-associated
genes in
13 male patients, but also in 5 female patients (51%). We
independently confirmed this new finding using chromogenic
in situ hybridization for X-and
Y-chromosomes
and
brightfield microscopy of the MOGHE clusters (Fig.1 A,
B). Immunofluorescence staining of the Y-chromosome
linked Neuroligin 4Y protein, a cell adhesion molecule
essential for synapse formation, also displayed increased
signal in those cases with an aberrant Y-chromosome
CNV profile (Fig.2 A, B).
Conclusion: In conclusion, all individuals from our
MOGHE cohort displayed either X-linked
SLC35A2 alterations,
a gain of the Y-chromosome
or both conditions
together suggesting that MOGHE is indeed a sex
chromosome-linked
disease entity. Further investigations
are required to better understand the pathomechanism
underlying altered sex chromosomes and epilepsy.

Authors with CRIS profile

Additional Organisation(s)

Involved external institutions

University of Edinburgh United Kingdom (GB) Universität Bielefeld Germany (DE) Schön Kliniken Germany (DE)

How to cite

APA:

Cecchini, E., Coras, R., Katoch, M., Kobow, K., Hartlieb, T., Bien, C.,... Hoffmann, L. (2024). Brain somatic mosaicism of sex chromosomes defines MOGHE. Epilepsia, 65, 50-51. https://doi.org/10.1111/epi.18151

MLA:

Cecchini, Erica, et al. "Brain somatic mosaicism of sex chromosomes defines MOGHE." Epilepsia 65 (2024): 50-51.

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