[Clinical characteristics and pathogenic variant analysis in a pedigree with syndromic hearing loss caused by likely pathogenic variants in the gene].

To investigate the pathogenic variants and function of a pedigree with syndromic hearing loss using high-throughput sequencing. Detailed medical history and pedigree history were inquired, and a pedigree chart was drawn. Hearing examinations were performed on this pedigree, and whole-exome sequencing and bioinformatics analysis were performed to screen for suspected pathogenic variants. Then, Sanger sequencing was used to test co-segregation in the family, and transcriptome sequencing was used to investigate the effect of a variant on splicing. The proband has auditory neuropathy combined with symptoms such as development delay, muscle weakness, and seizure. The patient carries two variants in (NM_024678.6), namely: c.779A>C (p.Glu260Ala) and c.372+3A>G (intronic variant), of which c.779A>C is inherited from the father and c.372+3A>G from the mother. Both variants have not been reported in the literature or included in any databases. Transcriptome sequencing results indicate that the c.372+3A>G variant leads to the skipping of the third exon during transcription. According to the American College of Medical Genetics and Genomics(ACMG) guidelines, the c.779A>C variant and c.372+3A>G are classified as likely pathogenic. Based on the patient's phenotype and genetic testing results, the proband has been diagnosed with combined oxidative phosphorylation deficiency 24(COXPD24). The pathogenic variants in the gene are the underlying cause of the patient's disease. The identification of novel variants enriches the mutational spectrum of the gene, providing evidence for further clarification of the relationship between and COXPD24.