A novel autosomal dominant variant in TMC1 and rare autosomal recessive variants in GJB2, SLC26A4 caused congenital hearing loss in Vietnamese children

Abstract

Background

Hearing loss in children can lead to consequences such as failure in speech, language, education and poor quality of life. This study investigated five Vietnamese families, one with all three children and others with one child suffered from congenital hearing loss to identify genetic cause of the disease.

Methods and results

Whole exome sequencing was performed for one proband of each family. Subsequently, Sanger sequencing was used for validation the genetic variants in the patients as well as other family members including parents and siblings. A novel variant in TMC1 (c.2209C > T) was detected in the affected child of family 1, which arose as a de novo mutation. In all three affected children of family 2, compound heterozygous variants were detected in SLC26A4 (c.754 T > C, c.1229C > T). In the affected children of family 4 and 5, compound heterozygous of GJB2 (c.109G > A, c.428G > A) and a homozygous deletion in GJB2 (c.235delC) were detected, respectively. In family 3, two genetic variants identified in deafness causing genes MYO7A (c.4795C > T) and MYO15A (c.7547C > T) of the patient in heterozygous state. Sangger sequencing identified only one pathogenic variant in each parent of family 2, 4 and 5. Similarly, existence of double heterozygote in MYO7A/MYO15A was not identified in the parents and remaining unaffected child in family 3.

Conclusions

This study contributed to expand genetic variants spectrum in Vietnamese hearing loss pediatrics. Identifying the genetic causes is crucial for early management of hearing loss patients and giving genetic counseling for further pregnancies of high-risk couples.