Affiliation:
1. Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration Wuhan China
2. Department of Otorhinolaryngology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China
3. Institute of Otorhinolaryngology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Abstract
AbstractBackgroundHereditary hearing loss is an important component of congenital hearing loss. MARVELD2 (OMIM ID:610572), located in the DFNB49 locus, which encodes a tight junction protein tricellulin playing an important role in the sensory epithelial barrier of the inner ear, may contribute to nonsyndromic autosomal recessive hereditary hearing loss.MethodsTwo Han Chinese pedigrees with hearing loss underwent clinical and genetic analyses. Variants were detected by targeted next‐generation sequencing and sequencing data were compared with the Human Genome Reference (GRCh 37/hg 19) to identify mutant genes and loci. Furthermore, online tools such as RDDC, SpliceAI, and REVEL were used to predict risks from different variants.ResultsBoth two probands failed neonatal hearing screening and were diagnosed with sensorineural hearing loss. A total of 3 mutations were detected in the two families, c.1331+1G>A, c.1325A>G, and c.782G>A. According to ACMG/AMP guidelines, they were judged to be pathogenic, uncertain significance, and uncertain significance, respectively.ConclusionsThese findings contribute to a better understanding of the relationship between different variants of MARVELD2 and hearing. This could further expand the spectrum of deafness gene mutations and contribute to deafness patient management and genetic counseling.
Funder
National Natural Science Foundation of China
Foundation for Innovative Research Groups of Hubei Province
National Key Research and Development Program of China