Clinical, genetic and transcriptomic characteristics of children with ACAN gene mutation
10.3760/cma.j.cn101070-20241219-00861
- VernacularTitle:ACAN基因变异病例的临床、遗传学及转录组学分析
- Author:
Xiaoyan WANG
1
;
Haiying WU
1
;
Rongrong XIE
1
;
Linqi CHEN
1
;
Xiuli CHEN
1
;
Ting CHEN
1
;
Hui SUN
1
;
Dandan ZHANG
1
;
Lili WANG
1
;
Bingyu YANG
1
;
Fengyun WANG
1
Author Information
1. 苏州大学附属儿童医院内分泌遗传代谢科，苏州 215003
- Publication Type:Journal Article
- Keywords:
Growth hormone;
Transcriptomics;
Familial short stature;
ACAN gene
- From:
Chinese Journal of Applied Clinical Pediatrics
2025;40(11):847-851
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To summarize the clinical and genetic characteristics of 23 children with pathogenic ACAN gene variants, enhance the understanding of this disorder, and explore possible regulatory mechanisms. Methods:A retrospective case series summary.The clinical characteristics and genetic analysis results of 23 children with ACAN gene variants treated in the Department of Endocrinology, Genetics and Metabolism, Children′s Hospital of Soochow University from January 2016 and September 2024 were analyzed retrospectively.Transcriptome sequencing was performed on peripheral blood samples from 3 of affected children and 3 age-matched healthy children as controls.Differentially expressed genes (DEGs) in the peripheral blood transcriptome profiles were identified.Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted to explore the potential signaling pathways involved. Results:Among the 23 cases, there were 13 males and 10 females, aged from 2 years and 8 months to 12 years old, with 11 cases presenting advanced bone age.Thirteen cases were treated with growth hormone (GH), including 6 cases who received concomitant gonadotropin-releasing hormone analogue therapy.The treatment duration ranged from 3 to 70 months, resulting in varying degrees of height improvement in all treated patients.Transcriptomic analysis identified 811 DEGs, with 516 up-regulated and 295 down-regulated.GO and KEGG enrichment analyses revealed that the heterozygous ACAN variants were significantly associated with FcγR-mediated phagocytosis, nuclear factor-κB signaling pathway, the intestinal immune network for IgA production, rheumatoid arthritis, and systemic lupus erythematosus signaling pathways. Conclusions:The predominant clinical manifestations of patients with ACAN gene variants are short stature and advanced bone age.Although GH provocation tests may indicate normal GH levels, GH therapy can be effective in improving height.Immune-related factors may play a role in the pathogenesis of this disorder.
