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Autosomal-recessive (AR) nonsyndromic hearing loss is usually prelingual and frequently results in severe hearing loss, although milder and progressive hearing loss forms also exist. GJB2 and SLC26A4 are the 2 most common AR genes.
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Autosomal-dominant (AD) nonsyndromic hearing loss is often postlingual and progressive. No single gene accounts for any significant proportion of AD hearing loss.
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High-throughput sequencing techniques, also called next-generation sequencing (NGS) or massively parallel
Genetics of Hearing Loss—Nonsyndromic
Section snippets
Key points
Autosomal-recessive genes
In AR inheritance, there is often no family history of hearing loss. Although AR SNHL is more common in families in which parents are related (consanguinity), they are not exclusive to such families, and most affected individuals have a negative history of consanguinity within the family tree. According to the hereditary hearing loss homepage, 60 genetic mutations have been identified causing nonsyndromic AR hearing loss.5
Autosomal-dominant genes
AD SNHL is much more easily identified from a multigenerational family history than AR SNHL. However, in contrast to AR SNHL in which 2 genes (GBJ2 and SLC26A4) account for a high proportion of cases, there is no single gene that accounts for any significant proportion of AD SNHL. Most nonsyndromic AD SNHL is postlingual and progressive, and some genes (COCH) may even cause adult-onset SNHL. According to the hereditary hearing loss homepage, 32 genetic mutations have been identified causing
POU3F4 (DFNX2)
POU3F4 is the most common genetic mutation causing X-linked nonsyndromic hearing loss. It results in a distinct radiological malformation characterized by cochlear hypoplasia and bulbous internal auditory canals. In addition to SNHL, there is often a conductive component to the hearing loss, caused by physiologic stapes fixation, which is not improved by stapes surgery and may cause a gusher of cerebrospinal fluid (CSF) if operated upon.44, 45 Mutations in 4 X-linked genes have been identified
A1555G
Mitochondrial disorders resulting in hearing loss are usually multisystemic and thus syndromic. However, one common nonsyndromic form of mitochondrial deafness is the A1555G mutation in the mitochondrial 12S ribosomal ribonucleic acid (rRNA) gene.46 The A1555G mutation may be present in up to 1 in 500 Caucasians, and can result in severe hearing loss from exposure to normal therapeutic levels of aminoglycosides.47 Because of their low cost and high availability, the use of aminoglycosides is
Next-generation or massively parallel sequencing
High-throughput sequencing techniques, also called next-generation sequencing (NGS) or massively parallel sequencing (MPS),2, 52, 53, 54, 55 now allow comprehensive testing of all known deafness-associated genes in a child presenting with congenital SNHL. Although complete sequencing of GJB2 could diagnose approximately 25% of all possible genetic hearing losses, utilization of NGS/MPS techniques appears to increase the diagnostic rate to around 50%.53, 56
The first study using MPS for diagnosis
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Advances in gene therapy hold promise for treating hereditary hearing loss
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2019, GenomicsCitation Excerpt :Hearing loss (HL) is one of the most common congenital impairments, occurring in approximately 1–2 in 1000 newborns worldwide [1,2].
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2023, World Journal of Clinical Pediatrics
Disclosure Statement: The authors have nothing to disclose.