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@ARTICLE{Alves:164828,
author = {Alves, C. A. P. F. and Sherbini, O. and D’Arco, F. and
Steel, D. and Kurian, M. A. and Radio, F. C. and Ferrero, G.
B. and Carli, D. and Tartaglia, M. and Balci, T. B. and
Powell-Hamilton, N. N. and Schrier Vergano, S. A. and
Reutter, H. and Hoefele, J. and Günthner, R. and Roeder, E.
R. and Littlejohn, R. O. and Lessel, D. and Lüttgen, S. and
Kentros, C. and Anyane-Yeboa, K. and Catarino, C. B. and
Mercimek-Andrews, S. and Denecke, Jannis and Lyons, M. J.
and Klopstock, Thomas and Bhoj, E. J. and Bryant, L. and
Vanderver, A.},
title = {{B}rain {A}bnormalities in {P}atients with {G}ermline
{V}ariants in {H}3{F}3 : {N}ovel {I}maging {F}indings and
{N}eurologic {S}ymptoms {B}eyond {S}omatic {V}ariants and
{B}rain {T}umors},
journal = {American journal of neuroradiology},
volume = {43},
number = {7},
issn = {0195-6108},
address = {Oak Brook, Ill.},
publisher = {Soc.},
reportid = {DZNE-2022-01272},
pages = {1048 - 1053},
year = {2022},
abstract = {Pathogenic somatic variants affecting the genes Histone 3
Family 3A and 3B (H3F3) are extensively linked to the
process of oncogenesis, in particular related to central
nervous system tumors in children. Recently, H3F3 germline
missense variants were described as the cause of a novel
pediatric neurodevelopmental disorder. We aimed to
investigate patterns of brain MR imaging of individuals
carrying H3F3 germline variants.Materials and methods: In
this retrospective study, we included individuals with
proved H3F3 causative genetic variants and available brain
MR imaging scans. Clinical and demographic data were
retrieved from available medical records. Molecular genetic
testing results were classified using the American College
of Medical Genetics criteria for variant curation. Brain MR
imaging abnormalities were analyzed according to their
location, signal intensity, and associated clinical
symptoms. Numeric variables were described according to
their distribution, with median and interquartile
range.Results: Eighteen individuals (10 males, $56\%)$ with
H3F3 germline variants were included. Thirteen of 18
individuals $(72\%)$ presented with a small posterior fossa.
Six individuals $(33\%)$ presented with reduced size and an
internal rotational appearance of the heads of the caudate
nuclei along with an enlarged and squared appearance of the
frontal horns of the lateral ventricles. Five individuals
$(28\%)$ presented with dysgenesis of the splenium of the
corpus callosum. Cortical developmental abnormalities were
noted in 8 individuals $(44\%),$ with dysgyria and
hypoplastic temporal poles being the most frequent
presentation.Conclusions: Imaging phenotypes in germline
H3F3-affected individuals are related to brain features,
including a small posterior fossa as well as dysgenesis of
the corpus callosum, cortical developmental abnormalities,
and deformity of lateral ventricles.},
keywords = {Brain: diagnostic imaging / Brain: pathology / Brain
Neoplasms: diagnostic imaging / Brain Neoplasms: genetics /
Brain Neoplasms: pathology / Child / Germ Cells: pathology /
Histones: genetics / Humans / Male / Malformations of
Cortical Development: pathology / Neurodevelopmental
Disorders: pathology / Retrospective Studies},
cin = {AG Höglinger 2},
ddc = {610},
cid = {I:(DE-2719)1111015},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC9262070},
pubmed = {pmid:35772801},
doi = {10.3174/ajnr.A7555},
url = {https://pub.dzne.de/record/164828},
}