Novel compound heterozygous mutations in the LARS2 gene in a Chinese family with hearing loss.

Background: Mutations in the LARS2 gene are correlated with Perrault syndrome, a rare autosomal recessive genetic disorder, that is typically characterized by sensorineural hearing loss and ovarian insufficiency.

Methods: Whole-exome sequencing and mutational analysis were employed to identify hearing loss-causing genes in a Chinese family from the Guangxi Zhuang Autonomous Region. Clinical phenotypes, audiological data, and color Doppler ultrasound of the family were collected, and a series of computer software were used to analyze the impact of genetic variations on protein structure and function.

Results: Novel compound heterozygous LARS2 variants, c.604G > A and c.703C > T, were linked to hearing loss in the family, the latter of which has not been reported in any public database. The proband and her brother in this family presented with hearing loss, while the parents had normal hearing. Additionally, the c.703C > T mutation is a nonsense mutation, leading to a significant loss of amino acids, while the c.604G > A mutation affects the secondary structure and side-chain structure of the protein.

Conclusion: These mutations expand the LARS2 mutation spectrum and provide a basis for the genetic diagnosis of Perrault syndrome and related hearing loss.