Gnathodiaphyseal dysplasia caused by mutations in ANO5
10.16352/j.issn.1001-6325.2024.11.1504
- VernacularTitle:ANO5突变导致颌骨长骨发育不良
- Author:
Chaoqun ZHENG
1
;
Geping CUI
;
Xiuzhi REN
;
Xiuli ZHAO
Author Information
1. 中国医学科学院基础医学研究所,北京协和医学院基础学院 疑难重症及罕见病全国重点实验室医学遗传学系,北京 100005
- Keywords:
gnathodiaphyseal dysplasia;
whole exome sequencing;
ANO5;
variants
- From:
Basic & Clinical Medicine
2024;44(11):1504-1509
- CountryChina
- Language:Chinese
-
Abstract:
Objective To identify the clinical features and pathogenic variants in two unrelated families with gna-thodiaphyseal dysplasia(GDD),a rare genetic bone disorder.Methods Facial and limb deformities and skeletal morphology were observed in the probands and their family members.Peripheral blood samples(3-4 mL)were col-lected from the probands and their parents.Genomic DNA was extracted by standard phenol-chloroform method.Whole exome sequencing(WES)was performed to screen for candidate pathogenic gene variants of the probands.PCR-Sanger sequencing was used to validate the candidate pathogenic variants in the probands and their family members.The pathogenic variants responsible for GDD in the target families were determined through co-segregation of the pathogenic variants in the affected families,evolutionary conservation at the mutation sites,population allele frequency analysis and bioinformatics analysis.Results Heterozygous missense variants in the ANO5 gene were identified in both GDD probands.In family 1,the pathogenic variant was c.1 066T＞G located in the exon 11 of the ANO5 gene,while in family 2,the pathogenic variant was c.1 553G＞A located in the exon 15 of the ANO5.These two variants resulted in the substitutions of amino acid cysteine with glycine at position 356(p.Cys356Gly)and amino acid glycine with glutamic acid at position 518(p.Gly518Glu)in the ANO5 protein,respectively.Conclusions This study first identified the pathogenic variant c.1 066T＞G(p.Cys356Gly)in Chinese population,provided important evidence for prediction of disease prognosis and development of potential prenatal genetic diagnosis.
