Table 3.

Autosomal Recessive Nonsyndromic Hearing Loss: Distinctive Features Associated with Selected Genes

GeneDistinctive Features
BDP1 HL can be progressive & postlingual.
CDH23 Assoc w/phenotypic spectrum incl AR nonsyndromic HL & AR syndromic HL (See Usher syndrome type I.)
EPS8L2 HL can be progressive & postlingual.
GJB2
  • Most common cause of severe-to-profound AR nonsyndromic HL in Asian & White populations. In contrast, biallelic GJB2 pathogenic variants essentially do not contribute to genetic HL in sub-Saharan African populations. 1
  • Assoc w/phenotypic spectrum incl AR (GJB2-DFNB) 2 & AD (GJB2-DFNA) 2 nonsyndromic HL
LOXHD1 HL can be progressive & postlingual.
MYO7A
PCDH15 Assoc w/phenotypic spectrum incl AR nonsyndromic HL & AR syndromic HL (See Usher syndrome type I.)
SLC26A4
  • HL can be pre- or postlingual, asymmetric, & progressive.
  • Assoc w/phenotypic spectrum incl AR nonsyndromic HL (nonsyndromic enlarged vestibular aqueduct [NSEVA]) & AR syndromic HL (Pendred syndrome [PDS]). When PDS/NSEVA are considered part of the same disease spectrum, prevalence rates are very high, as pathogenic variants in SLC26A4 are the 3rd most frequent cause of HL (see Pendred Syndrome / Nonsyndromic Enlarged Vestibular Aqueduct).
STRC
  • Biallelic STRC pathogenic variants are the most common cause of mild-to-moderate AR HL, and the 2nd most common cause of AR HL overall. 3
  • Biallelic contiguous gene deletions at chromosome 15q15.3 that include STRC & CATSPER2 are assoc w/deafness-infertility syndrome (see CATSPER-Related Male Infertility).
TECTA Assoc w/phenotypic spectrum incl AR & AD nonsyndromic HL
TMC1
TMPRSS3 HL can be progressive & postlingual.
USH1C Assoc w/phenotypic spectrum incl AR nonsyndromic HL & AR syndromic HL (See Usher syndrome type I.)
WHRN Assoc w/phenotypic spectrum incl AR nonsyndromic HL & AR syndromic HL (See Usher syndrome type II.)

AD = autosomal dominant; AR = autosomal recessive; HL = hearing loss

1.
2.

Nonsyndromic deafness loci are designated DFN (for DeaFNess) and further classified by mode of inheritance (e.g., DFNA: autosomal dominant & DFNB: autosomal recessive).

3.

From: Genetic Hearing Loss Overview

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