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Mosaicism in BRPF1-Related Neurodevelopmental Disorder: Report of Two Sisters and Literature Review

Bromodomain and PHD finger containing 1 (BRPF1)-related neurodevelopmental disorder is characterized by intellectual disability, developmental delay, hypotonia, dysmorphic facial features, ptosis, and blepharophimosis. Both de novo and inherited pathogenic variants have been previously reported in a...

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Detalles Bibliográficos
Autores principales: Bayanbold, Khaliunaa, Younger, Georgianne, Darbro, Benjamin, Sidhu, Alpa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10632058/
https://www.ncbi.nlm.nih.gov/pubmed/37946714
http://dx.doi.org/10.1155/2023/1692422
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author Bayanbold, Khaliunaa
Younger, Georgianne
Darbro, Benjamin
Sidhu, Alpa
author_facet Bayanbold, Khaliunaa
Younger, Georgianne
Darbro, Benjamin
Sidhu, Alpa
author_sort Bayanbold, Khaliunaa
collection PubMed
description Bromodomain and PHD finger containing 1 (BRPF1)-related neurodevelopmental disorder is characterized by intellectual disability, developmental delay, hypotonia, dysmorphic facial features, ptosis, and blepharophimosis. Both de novo and inherited pathogenic variants have been previously reported in association with this disorder. We report two affected female siblings with a novel variant in BRPF1 c.2420_2433del (p.Q807Lfs∗27) identified through whole-exome sequencing. Their history of mild intellectual disability, speech delay, attention deficient hyperactivity disorder (ADHD), and ptosis align with the features previously reported in the literature. The absence of the BRPF1 variant in parental buccal samples provides evidence of a de novo frameshift pathogenic variant, most likely as a result of parental gonadal mosaicism, which has not been previously reported. The frameshift pathogenic variant reported here lends further support to haploinsufficiency as the underlying mechanism of disease. We review the literature, compare the clinical features seen in our patients with others reported, and explore the possibility of genotype-phenotype correlation based on the location of pathogenic variants in BRPF1. Our study helps to summarize available knowledge and report the first case of a de novo frameshift pathogenic variant in BRPF1 in two siblings with this neurodevelopmental disorder.
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spelling pubmed-106320582023-11-09 Mosaicism in BRPF1-Related Neurodevelopmental Disorder: Report of Two Sisters and Literature Review Bayanbold, Khaliunaa Younger, Georgianne Darbro, Benjamin Sidhu, Alpa Case Rep Genet Case Report Bromodomain and PHD finger containing 1 (BRPF1)-related neurodevelopmental disorder is characterized by intellectual disability, developmental delay, hypotonia, dysmorphic facial features, ptosis, and blepharophimosis. Both de novo and inherited pathogenic variants have been previously reported in association with this disorder. We report two affected female siblings with a novel variant in BRPF1 c.2420_2433del (p.Q807Lfs∗27) identified through whole-exome sequencing. Their history of mild intellectual disability, speech delay, attention deficient hyperactivity disorder (ADHD), and ptosis align with the features previously reported in the literature. The absence of the BRPF1 variant in parental buccal samples provides evidence of a de novo frameshift pathogenic variant, most likely as a result of parental gonadal mosaicism, which has not been previously reported. The frameshift pathogenic variant reported here lends further support to haploinsufficiency as the underlying mechanism of disease. We review the literature, compare the clinical features seen in our patients with others reported, and explore the possibility of genotype-phenotype correlation based on the location of pathogenic variants in BRPF1. Our study helps to summarize available knowledge and report the first case of a de novo frameshift pathogenic variant in BRPF1 in two siblings with this neurodevelopmental disorder. Hindawi 2023-11-01 /pmc/articles/PMC10632058/ /pubmed/37946714 http://dx.doi.org/10.1155/2023/1692422 Text en Copyright © 2023 Khaliunaa Bayanbold et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Case Report
Bayanbold, Khaliunaa
Younger, Georgianne
Darbro, Benjamin
Sidhu, Alpa
Mosaicism in BRPF1-Related Neurodevelopmental Disorder: Report of Two Sisters and Literature Review
title Mosaicism in BRPF1-Related Neurodevelopmental Disorder: Report of Two Sisters and Literature Review
title_full Mosaicism in BRPF1-Related Neurodevelopmental Disorder: Report of Two Sisters and Literature Review
title_fullStr Mosaicism in BRPF1-Related Neurodevelopmental Disorder: Report of Two Sisters and Literature Review
title_full_unstemmed Mosaicism in BRPF1-Related Neurodevelopmental Disorder: Report of Two Sisters and Literature Review
title_short Mosaicism in BRPF1-Related Neurodevelopmental Disorder: Report of Two Sisters and Literature Review
title_sort mosaicism in brpf1-related neurodevelopmental disorder: report of two sisters and literature review
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10632058/
https://www.ncbi.nlm.nih.gov/pubmed/37946714
http://dx.doi.org/10.1155/2023/1692422
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