Novel PAX1 mutation identified in autosomal dominant otofaciocervical syndrome 2 with new phenotypes
10.3760/cma.j.cn115330-20240723-00443
- VernacularTitle:PAX1基因新杂合突变导致的伴发新表型的常染色体显性遗传耳-面-颈综合征2型
- Author:
Ying CHEN
1
;
Run YANG
;
Nai′er LIN
;
Qingxiong YU
;
Xin CHEN
;
Tianyu ZHANG
;
Jing MA
Author Information
1. 复旦大学附属眼耳鼻喉科医院眼耳鼻整形外科 耳鼻喉研究院，上海 200031
- Publication Type:Journal Article
- Keywords:
Ear malformation;
Otofaciocervical syndrome 2;
PAX1;
Whole exome sequencing
- From:
Chinese Journal of Otorhinolaryngology Head and Neck Surgery
2025;60(7):815-823
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To determine the diagnosis of microtia-associated syndrome through genetic testing.Methods:Peripheral venous blood samples were collected from members of a two-generation family with a syndrome associated with ear malformations (3 patients and 1 normal control). Pathogenic mutations were identified using whole exome sequencing analysis, Sanger sequencing validation, and bioinformatics analysis. Based on the genetic diagnosis and a review of the literatures, the patients′ clinical phenotypes were thoroughly evaluated to confirm the clinical diagnosis.Results:All three patients carried a novel heterozygous insertion mutation (c.1171_1172insGGCC: p.Pro391fs) in the paired box 1 ( PAX1) gene. This mutation showed genotype-phenotype co-segregation within the family and was predicted to be pathogenic. Consequently, the family was diagnosed with autosomal dominant otofaciocervical syndrome 2. The clinical phenotypes of the patients included not only ear malformations and conductive hearing loss but also branchial cleft fistula, preauricular fistula, bilateral facial asymmetry, spinal deformities, and short stature, which were major symptoms of otofaciocervical syndrome 2. Imaging also revealed previously unreported phenotypes, including parotid gland malformation and facial nerve dysplasia. Conclusion:The heterozygous insertion in PAX1 (c.1171_1172insGGCC: p.Pro391fs) found in this family causes otomandibular-cervical syndrome type 2 in an autosomal dominant manner, leading to congenital anomalies affecting external and middle ear, craniofacial region, and spine.
