Analysis of clinical phenotypes and genotypes of congenital deafness caused by rare variants in GJB2

Xuxu Zhao ¹ Chi Huan ^{2,3,4,5,6,7,8,9} Yan Bai ^{2,3,4,5,6,7,8,9} Yu Lu ¹⁰ Wenyu Xiong ¹⁰ Houyong Kang ¹¹ Cheng Zhang ^{2,3,4,5,6,7,8,9*}

• ¹ Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Chongqing Medical University, chognqing, China
• ² Department of Otolaryngology, Children’s Hospital of Chongqing Medical University, Chongqing, China
• ³ National Clinical Research Center for Child Health and Disorders, Chongqing, China
• ⁴ Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China
• ⁵ Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, China
• ⁶ Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China
• ⁷ Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing, China
• ⁸ Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing, China
• ⁹ Chongqing Engineering Research Center of Stem Cell Therapy., chognqing, China
• ¹⁰ West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
• ¹¹ Department of Otorhinolaryngology, Head and Neck Surgery，Second Affiliated Hospital of Chongqing Medical University., Chongqing, China

Objective: This study aims to analyze a genetic family with the GJB2 gene c.551G>A (p.R184Q) variant, exploring the relationship between its genotype and clinical phenotype, and summarizing the inheritance pattern and clinical features associated with this locus. Methods: Detailed medical history collection and physical examinations were conducted for the proband and their family members. Audiological assessments and genetic sequencing analyses were performed on some members.Additionally, a review of existing literature concerning GJB2 c.551G>A (p.R184Q) was conducted. Results: The proband, along with their father and paternal grandmother, carried the heterozygous mutation GJB2 c.551G>A, all exhibiting moderate to profound bilateral prelingual sensorineural deafness. Notably, the proband also presented symptoms of skin dryness and nail abnormalities characteristic of syndromic hearing loss. Conclusion: The GJB2 c.551G>A mutation not only leads to severe hearing loss but may also be associated with syndromic hearing loss, expanding our understanding of the clinical spectrum associated with this variant.