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Agenesis of the Corpus Callosum with Facial Dysmorphism and Intellectual Disability in Sibs Associated with Compound Heterozygous KDM5B Variants

We studied a family in which the first-born child, a girl, had developmental delay, facial dysmorphism, and agenesis of the corpus callosum (ACC). The subsequent pregnancy was interrupted as the fetus was found to be also affected by ACC. Both cases were heterozygous for two KDM5B variants predictin...

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Autores principales: Lebon, Sébastien, Quinodoz, Mathieu, Peter, Virginie G., Gengler, Carole, Blanchard, Gaëlle, Cina, Viviane, Campos-Xavier, Belinda, Rivolta, Carlo, Superti-Furga, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467522/
https://www.ncbi.nlm.nih.gov/pubmed/34573379
http://dx.doi.org/10.3390/genes12091397
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author Lebon, Sébastien
Quinodoz, Mathieu
Peter, Virginie G.
Gengler, Carole
Blanchard, Gaëlle
Cina, Viviane
Campos-Xavier, Belinda
Rivolta, Carlo
Superti-Furga, Andrea
author_facet Lebon, Sébastien
Quinodoz, Mathieu
Peter, Virginie G.
Gengler, Carole
Blanchard, Gaëlle
Cina, Viviane
Campos-Xavier, Belinda
Rivolta, Carlo
Superti-Furga, Andrea
author_sort Lebon, Sébastien
collection PubMed
description We studied a family in which the first-born child, a girl, had developmental delay, facial dysmorphism, and agenesis of the corpus callosum (ACC). The subsequent pregnancy was interrupted as the fetus was found to be also affected by ACC. Both cases were heterozygous for two KDM5B variants predicting p (Ala635Thr) and p (Ser1155AlafsTer4) that were shown to be in trans. KDM5B variants have been previously associated with moderate to severe developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and dysmorphism in a few individuals, but the pathogenetic mechanisms are not clear yet as patients with both monoallelic and biallelic variants have been observed. Interestingly, one individual has previously been reported with ACC and severe ID in association with biallelic KDM5B variants. Together with the observations in this family, this suggests that agenesis of the corpus callosum may be part of the phenotypic spectrum associated with KDM5B variants and that the KDM5B gene should be included in gene panels to clarify the etiology of ACC both in the prenatal and postnatal setting.
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spelling pubmed-84675222021-09-27 Agenesis of the Corpus Callosum with Facial Dysmorphism and Intellectual Disability in Sibs Associated with Compound Heterozygous KDM5B Variants Lebon, Sébastien Quinodoz, Mathieu Peter, Virginie G. Gengler, Carole Blanchard, Gaëlle Cina, Viviane Campos-Xavier, Belinda Rivolta, Carlo Superti-Furga, Andrea Genes (Basel) Case Report We studied a family in which the first-born child, a girl, had developmental delay, facial dysmorphism, and agenesis of the corpus callosum (ACC). The subsequent pregnancy was interrupted as the fetus was found to be also affected by ACC. Both cases were heterozygous for two KDM5B variants predicting p (Ala635Thr) and p (Ser1155AlafsTer4) that were shown to be in trans. KDM5B variants have been previously associated with moderate to severe developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and dysmorphism in a few individuals, but the pathogenetic mechanisms are not clear yet as patients with both monoallelic and biallelic variants have been observed. Interestingly, one individual has previously been reported with ACC and severe ID in association with biallelic KDM5B variants. Together with the observations in this family, this suggests that agenesis of the corpus callosum may be part of the phenotypic spectrum associated with KDM5B variants and that the KDM5B gene should be included in gene panels to clarify the etiology of ACC both in the prenatal and postnatal setting. MDPI 2021-09-10 /pmc/articles/PMC8467522/ /pubmed/34573379 http://dx.doi.org/10.3390/genes12091397 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Lebon, Sébastien
Quinodoz, Mathieu
Peter, Virginie G.
Gengler, Carole
Blanchard, Gaëlle
Cina, Viviane
Campos-Xavier, Belinda
Rivolta, Carlo
Superti-Furga, Andrea
Agenesis of the Corpus Callosum with Facial Dysmorphism and Intellectual Disability in Sibs Associated with Compound Heterozygous KDM5B Variants
title Agenesis of the Corpus Callosum with Facial Dysmorphism and Intellectual Disability in Sibs Associated with Compound Heterozygous KDM5B Variants
title_full Agenesis of the Corpus Callosum with Facial Dysmorphism and Intellectual Disability in Sibs Associated with Compound Heterozygous KDM5B Variants
title_fullStr Agenesis of the Corpus Callosum with Facial Dysmorphism and Intellectual Disability in Sibs Associated with Compound Heterozygous KDM5B Variants
title_full_unstemmed Agenesis of the Corpus Callosum with Facial Dysmorphism and Intellectual Disability in Sibs Associated with Compound Heterozygous KDM5B Variants
title_short Agenesis of the Corpus Callosum with Facial Dysmorphism and Intellectual Disability in Sibs Associated with Compound Heterozygous KDM5B Variants
title_sort agenesis of the corpus callosum with facial dysmorphism and intellectual disability in sibs associated with compound heterozygous kdm5b variants
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467522/
https://www.ncbi.nlm.nih.gov/pubmed/34573379
http://dx.doi.org/10.3390/genes12091397
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