Analysis of clinical characteristics and genetic etiology in one case of a child with Osteopathia Striata with Cranial Sclerosis caused by AMER1 gene variation
10.3760/cma.j.cn511374-20250407-00206
- VernacularTitle:AMER1基因变异致条纹状骨病伴颅骨硬化症患儿1例的临床特征及遗传学病因分析
- Author:
Huichun ZHANG
1
;
Wenhan YIN
;
Yanli WANG
;
Baiyun CHEN
;
Chao GAO
;
Lei LIU
;
Yanhong WANG
;
Xiaoman ZHANG
;
Linfei LI
Author Information
1. 郑州大学附属儿童医院，河南省儿童医院郑州儿童医院康复医学科，郑州 450018
- Publication Type:Journal Article
- Keywords:
Osteopathia striata with cranial sclerosis;
Hybrid frameshift mutation;
AMER1 gene;
De novo variant
- From:
Chinese Journal of Medical Genetics
2025;42(9):1120-1125
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical characteristics and genetic etiology of a child with Osteopathia striata with cranial sclerosis (OSCS) due to variant of AMER1 gene. Methods:A child presented at the Affiliated Children′s Hospital of Zhengzhou University in July 2024 due to growth and development retardation was selected as the study subject. A retrospective study was conducted to collect the child′s clinical data. Peripheral blood samples (2 mL each) were collected from the child and her parents, and genomic DNA was extracted for whole exome sequencing (WES). Sanger sequencing was used for the verification of candidate variants. The pathogenicity of variant was rated according to the guidelines from American College of Medical Genetics and Genomics (ACMG). The study has been approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No.: 2024-108-001).Results:The patient, a 4-year-and-10-month-old girl, presented with global developmental delay, short stature, cleft palate, distinct facial features, and hearing impairment. WES revealed that she has harbored a heterozygous c. 790_794dup (p.Cys265Trpfs*19) variant of the AMER1 gene, which was not detected in either parent. Based on the guidelines from ACMG, the gene variant was classified as pathogenic (PVS1 + PS2 + PM2_supporting). As the result of a non-triplet base insertion in the coding region of the AMER1 gene, it has converted a codon originally encoding an amino acid into a stop codon, and led to a truncated protein, causing severe alteration and dysfunction of the protein. Conclusion:The child was diagnosed with OSCS for clinical features such as global developmental delay, short stature, cleft palate, distinctive facial features, and hearing impairment, for which the de novo heterozygous frameshift variant AMER1: c. 790_794dup (p.Cys265Trpfs*19) may be accountable. Above finding has expanded the mutational spectrum of OSCS and provided a basis for genetic counseling and prenatal diagnosis for the family.
