Genetic analysis of two children with Coffin-Siris syndrome due to variants of ARID1B gene / 中华医学遗传学杂志
Chinese Journal of Medical Genetics
;
(6): 67-74, 2024.
Artigo
em Chinês
| WPRIM
| ID: wpr-1009355
ABSTRACT
OBJECTIVE@#To explore the genetic basis of two children with unexplained psychomotor developmental delay and facial dysmorphisms suggestive of Coffin-Siris syndrome (CSS).@*METHODS@#A boy and a girl suspected for CSS at the 980th Hospital of the People's Liberation Army Joint Service Support Force respectively in July 2019 and January 2021, and seven members from their families, were selected as the study subjects. Clinical data and family history of the children were collected, and detailed physical examination was carried out, in addition with laboratory and related auxiliary examinations. Potential variants and copy number variations (CNVs) were detected by whole exome sequencing (WES) and copy number variation sequencing (CNV-seq).@*RESULTS@#Child 1, an 8-month-old female, had featured microcephaly, atrial septal defect, curving of fifth finger/toe, and low limb muscle tone. Child 2 was a 2.5-year-old male with language delay, social impairment, dense hair but no curving of the fifth fingers. Genetic testing revealed that child 1 had loss of heterozygosity for exons 8 to 21 of the ARID1B gene, which was unreported previously. Family verification showed that both of her parents were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and American Society of Molecular Pathology (AMP), the variant was rated as pathogenic (PVS1+PS2+PM2-supporting). Child 2 was found to harbor a heterozygous c.4263-6 (IVS17) T>G variant of the ARID1B gene. Transcriptome sequencing confirmed that the variant can affect the normal splicing, resulting in retention of a 5 bp sequence in intron 17. Family verification showed that both of his parents were of the wild type. Based on the guidelines from the ACMG, the variant was rated as pathogenic (PS2+PM2-supporting+PP3+PS3).@*CONCLUSION@#WES and RNA-seq have confirmed the diagnosis of CSS in both children. Discovery of the novel variants has expanded the spectrum of pathogenic mutations underlying CSS, and provided a basis for the genetic counseling.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fatores de Transcrição
/
Anormalidades Múltiplas
/
Proteínas de Ligação a DNA
/
Variações do Número de Cópias de DNA
/
Deficiência Intelectual
/
Micrognatismo
/
Mutação
Limite:
Criança, pré-escolar
/
Feminino
/
Humanos
/
Lactente
/
Masculino
Idioma:
Chinês
Revista:
Chinese Journal of Medical Genetics
Ano de publicação:
2024
Tipo de documento:
Artigo
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