Genome-wide epigenetic signatures facilitated the variant classification of the PURA gene and uncovered the pathomechanism of PURA-related neurodevelopmental disorders.
Genet Med
; 26(8): 101167, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38770750
ABSTRACT
PURPOSE:
Rare genetic variants in the PURA gene cause the PURA-related neurodevelopmental disorder (PURA-NDD), characterized by neonatal abnormalities and developmental delay. Using genome-wide DNA methylation analysis on patients with PURA variants, we aim to establish a PURA-NDD-specific methylation profile and provide further insights on the molecular basis of the PURA-NDD.METHODS:
Twenty three individuals (including 12 unpublished) carrying PURA variants were enrolled. We conducted the Illumina Infinium EPIC microarray analysis in 17 PURA-NDD individuals. In vitro experiments were performed to examine how PURA variants affect Pur-a expression.RESULTS:
Additional phenotypes in 12 newly identified patients were described in this study. Genome-wide DNA methylation analysis unveiled distinctive methylation profiles to PURA-NDD, and the established classifier can reclassify PURA variants of uncertain significance. Patients bearing PURA hapoloinsufficient and missense variants have comparable DNA methylation profiles, and cells expressing these PURA variants showed consistent Pur-a downregulation, suggesting a haploinsufficiency mechanism.CONCLUSION:
Patients with PURA-NDD exhibit a specific episignature, which has potential to aid identification and diagnosis of PURA-NDD patients and offer implications for further functional investigations.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metilação de DNA
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Epigênese Genética
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Transtornos do Neurodesenvolvimento
Limite:
Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Genet Med
/
Genet. med
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Genetics in medicine
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China