Reproductive guidance through prenatal diagnosis and genetic counseling for recessive hereditary hearing loss in high-risk families

Abstract

Objective: To evaluate the accuracy and validity of our protocol for prenatal diagnosis and genetic counseling in high-risk families at a clinic.

Methods: Fifteen unrelated families with recessive nonsyndromic hearing loss (NSHL) in their family history and a positive attitude towards prenatal diagnosis were recruited in the present study. According to genetic information for each family, Sanger sequencing, fluorescence polymerase chain reaction (PCR)-based congenital deafness gene detection kit and multiple PCR-based target gene capture and high-throughput sequencing were used. Genetic counseling was offered to all participating families by genetic counselors and otologists. Prenatal diagnosis was provided to families with detected pathogenic mutations and who were expected to participate in subsequent prenatal diagnosis.

Results: In this study, confirmed pathogenic mutations were detected in eight families, who were defined as high-risk families. These families all participated in prenatal diagnosis with positive attitudes. One novel variant (c.1687dupA) in the SLC264 gene was detected in a family. Through genetic counseling, the recurrence probability of NSHL in fetuses was 25% in six families, 0% in one family, and 50% in one family. The results of fetal DNA detection showed that one fetal variant was wild type, three were heterozygous mutations in SLC26A4, and one was a compound heterozygous mutation in SLC26A4. Two variants were heterozygous mutations in GJB2, and one was a homozygous mutation in GJB2. According to the test results for fetal DNA, prenatal diagnosis found that six fetuses had normal hearing, whereas two fetuses suffered from NSHL. After birth, six infants predicted to have normal hearing passed a newborn hearing screening test and two infants predicted to have NSHL were diagnosed with NSHL and received cochlear implants.

Conclusion: Our protocol for prenatal diagnosis and genetic counseling provides detailed information that can assist couples in high-risk families in preparing for infant arrival and future family planning. For the affected neonates, prenatal diagnosis and genetic counseling achieve an "early screening, early diagnosis, early intervention" strategy.

Keywords: Genes; Genetic counseling; Prenatal diagnosis; Recessive; Sensorineural hearing loss.