Integrating whole-genome sequencing and transcriptomic findings in the diagnosis and management of Coffin-Siris syndrome.
Brain Dev
; 45(9): 495-504, 2023 Oct.
Article
en En
| MEDLINE
| ID: mdl-37302973
ABSTRACT
INTRODUCTION:
Although the whole-exome sequencing (WES) approach has been widely used in clinic, many rare diseases with syndromic and nonsyndromic neurological manifestations remain undiagnosed. Coffin-Siris syndrome (CSS) is a rare autosomal dominant genetic disease characterized by neurodevelopmental delay. A suspected diagnosis can be made based on the typical CSS clinical features; however, molecular genetic testing is necessary for a confirmed diagnosis.OBJECTIVES:
Three CSS-like patients with negative results in the WES and chromosomal microarray analysis (CMA) were recruited in this study.METHODS:
We used whole-genome sequencing (WGS) technology to sequence the peripheral blood of the three families. To further explore the possible pathogenesis of CSS, we performed RNA-sequencing (RNA-seq).RESULTS:
WGS identified the three CSS patients were carrying de novo copy number variants of the ARID1B gene, which have not been reported before. RNA-seq identified 184 differentially expressed genes (DEGs), with 116 up-regulated and 68 down-regulated. Functional annotation of DEGs showed that two biological processes (immune response, chemokine activity) and two signaling pathways (cytokine-cytokine receptor interaction, chemokine activity) were highlighted. We speculated that ARID1B deficiency might trigger abnormal immune responses, which may be involved in the pathophysiologic mechanisms of CSS.CONCLUSION:
Our research provided further support for WGS application in CSS diagnosis and made an investigational approach for the underlying mechanisms of CSS.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Deformidades Congénitas de la Mano
/
Discapacidad Intelectual
/
Micrognatismo
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Brain Dev
Año:
2023
Tipo del documento:
Article
País de afiliación:
China