Integrated omics analyses clarifies ATRX copy number variant of uncertain significance.
J Hum Genet
; 69(2): 101-105, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-37904029
ABSTRACT
Partial duplications of genes can be challenging to detect and interpret and, therefore, likely represent an underreported cause of human disease. X-linked dominant variants in ATRX are associated with Alpha-thalassemia/impaired intellectual development syndrome, X-linked (ATR-X syndrome), a clinically heterogeneous disease generally presenting with intellectual disability, hypotonia, characteristic facies, genital anomalies, and alpha-thalassemia. We describe an affected male with a de novo hemizygous intragenic duplication of ~43.6 kb in ATRX, detected by research genome sequencing following non-diagnostic clinical testing. RNA sequencing and DNA methylation episignature analyses were central in variant interpretation, and this duplication was subsequently interpreted as disease-causing. This represents the smallest reported tandem duplication within ATRX associated with disease. This case demonstrates the diagnostic utility of integrating multiple omics technologies, which can ultimately lead to a definitive diagnosis for rare disease patients.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Talassemia alfa
/
Deficiência Intelectual Ligada ao Cromossomo X
/
Deficiência Intelectual
Limite:
Humans
/
Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article