Clinical characteristics and pathogenic variant analysis of NOG-related symphangism spectrum disor-der
10.3969/j.issn.1006-7299.2025.05.003
- VernacularTitle:NOG基因相关指间关节粘连谱系障碍的临床特征和致病变异分析
- Author:
Xiaoqian YANG
1
;
Xiaosai ZHANG
;
Jinhui ZHANG
;
Shuping SUN
;
Hongen XU
;
Bei CHEN
Author Information
1. 郑州大学第一附属医院耳科(郑州 450052)
- Publication Type:Journal Article
- Keywords:
Proximal symphalangism;
Multipe synostoes syndrome-1;
NOG gene;
Conductive hearing loss
- From:
Journal of Audiology and Speech Pathology
2025;33(5):423-428
- CountryChina
- Language:Chinese
-
Abstract:
Objective To analyze the clinical phenotypes and genetic variants of three families with NOG-re-lated symphalangism spectrum disorder(NOG-SSD).Methods Clinical data of 11 family members from three NOG-SSD families were retrospectively analyzed,including medical history,physical examination,imaging studies,and audiological evaluations.Genomic DNA was extracted from peripheral blood samples of family members for whole-exome sequencing.Results Among the 11 family members,four exhibited mixed or conductive hearing loss.Probands from family 1 and 2 presented with mixed hearing loss,proximal symphalangism,flexion impairment of the fifth interphalangeal joint,and absence of skin creases.The proband and her mother in family 3 displayed con-ductive/mixed hearing loss,proximal symphalangism,and characteristic facial features(semicylindrical nose,hypo-plastic alae nasi,and thin upper lip with vermilion border).Whole-exome sequencing identified pathogenic variants in the NOG gene(NM_005450.6)in all three families.Family 1 and 2 harbored the novel missense variant c.236T＞A(p.Met79Lys)and nonsense variant c.666C＞G(p.Tyr222Ter),respectively,while family 3 carried the frameshift variant c.31del(p.Leu11SerfsTer51).All three variants were classified as pathogenic or likely pathogen-ic and have not been previously reported.Patients in family 1 and 2 were diagnosed with proximal symphalangism-1(SYM 1),whereas those in family 3 were diagnosed with multiple synostoses syndrome-1(SYNS1).Conclusion The NOG gene variants c.236T＞A,c.666C＞G,and c.31del are causative for NOG-SSD in these three families.
