TY  - INPR
UR  - http://dx.doi.org/10.1038/s41431-024-01610-1
JF  - European Journal of Human Genetics
N2  - Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1-4]. This syndrome is characterized by developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, and abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative syndrome caused by de novo heterozygous variants in either H3-3A or H3-3B [1-4]. Here, we analyze the data of the 58 previously published individuals along 38 unpublished, unrelated individuals. In this larger cohort of 96 people, we identify causative missense, synonymous, and stop-loss variants. We also expand upon the phenotypic characterization by elaborating on the neurodevelopmental component of BLBS. Notably, phenotypic heterogeneity was present even amongst individuals harboring the same variant. To explore the complex phenotypic variation in this expanded cohort, the relationships between syndromic phenotypes with three variables of interest were interrogated: sex, gene containing the causative variant, and variant location in the H3.3 protein. While specific genotype-phenotype correlations have not been conclusively delineated, the results presented here suggest that the location of the variants within the H3.3 protein and the affected gene (H3-3A or H3-3B) contribute more to the severity of distinct phenotypes than sex. Since these variables do not account for all BLBS phenotypic variability, these findings suggest that additional factors may play a role in modifying the phenotypes of affected individuals. Histones are poised at the interface of genetics and epigenetics, highlighting the potential role for gene-environment interactions and the importance of future research.
PB  - Springer Science and Business Media LLC
Y1  - 2024/04/27/
A1  - Layo-Carris, Dana E
A1  - Lubin, Emily E
A1  - Sangree, Annabel K
A1  - Clark, Kelly J
A1  - Durham, Emily L
A1  - Gonzalez, Elizabeth M
A1  - Smith, Sarina
A1  - Angireddy, Rajesh
A1  - Wang, Xiao Min
A1  - Weiss, Erin
A1  - Mendoza-Londono, Roberto
A1  - Dupuis, Lucie
A1  - Damseh, Nadirah
A1  - Velasco, Danita
A1  - Valenzuela, Irene
A1  - Codina-Solà, Marta
A1  - Ziats, Catherine
A1  - Have, Jaclyn
A1  - Clarkson, Katie
A1  - Steel, Dora
A1  - Kurian, Manju
A1  - Barwick, Katy
A1  - Carrasco, Diana
A1  - Dagli, Aditi I
A1  - Nowaczyk, MJM
A1  - Han?árová, Miroslava
A1  - Bendová, ?árka
A1  - Prchalova, Darina
A1  - Sedlá?ek, Zden?k
A1  - Baxová, Alica
A1  - Nowak, Catherine Bearce
A1  - Douglas, Jessica
A1  - Chung, Wendy K
A1  - Longo, Nicola
A1  - Platzer, Konrad
A1  - Klöckner, Chiara
A1  - Averdunk, Luisa
A1  - Wieczorek, Dagmar
A1  - Krey, Ilona
A1  - Zweier, Christiane
A1  - Reis, Andre
A1  - Balci, Tugce
A1  - Simon, Marleen
A1  - Kroes, Hester Y
A1  - Wiesener, Antje
A1  - Vasileiou, Georgia
A1  - Marinakis, Nikolaos M
A1  - Veltra, Danai
A1  - Sofocleous, Christalena
A1  - Kosma, Konstantina
A1  - Traeger Synodinos, Joanne
A1  - Voudris, Konstantinos A
A1  - Vuillaume, Marie-Laure
A1  - Gueguen, Paul
A1  - Derive, Nicolas
A1  - Colin, Estelle
A1  - Battault, Clarisse
A1  - Au, Billie
A1  - Delatycki, Martin
A1  - Wallis, Mathew
A1  - Gallacher, Lyndon
A1  - Majdoub, Fatma
A1  - Smal, Noor
A1  - Weckhuysen, Sarah
A1  - Schoonjans, An-Sofie
A1  - Kooy, R Frank
A1  - Meuwissen, Marije
A1  - Cocanougher, Benjamin T
A1  - Taylor, Kathryn
A1  - Pizoli, Carolyn E
A1  - McDonald, Marie T
A1  - James, Philip
A1  - Roeder, Elizabeth R
A1  - Littlejohn, Rebecca
A1  - Borja, Nicholas A
A1  - Thorson, Willa
A1  - King, Kristine
A1  - Stoeva, Radka
A1  - Suerink, Manon
A1  - Nibbeling, Esther
A1  - Baskin, Stephanie
A1  - L E Guyader, Gwenaël
A1  - Kaplan, Julie
A1  - Muss, Candace
A1  - Carere, Deanna Alexis
A1  - Bhoj, Elizabeth JK
A1  - Bryant, Laura M
SN  - 1018-4813
TI  - Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals
AV  - public
N1  - This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ID  - discovery10191954
ER  -