**2.4 Age of onset**

On the basis of the age of onset, HL is divided into the following types:


Genetics of Hearing Loss 215

are inherited as autosomal recessive [Tekin et al., 2001]. 10-20% of cases are inherited as autosomal dominant and 1-5% are X-linked recessive. Approximately, 1% of human genes, i.e 200 to 250 genes are responsible for hereditary HL [Finsterer & Fellinger, 2005]. So far, more than one hundred loci and 55 genes have identified which are involved in

A high frequency of genetic HL occurs without any abnormality in other organs classified as

Variety of protein coding genes such as gap junctions (connexin encoding genes), motor proteins (myosins) cytoskeletal (e.g. actin), ion channels, structural proteins (Tectorin alpha, Otoancorin, Stereocilin, etc), transcription factors (POU3F4, POU4F3 and Eyes absent 4 or EYA4), and additionally microRNA genes are involved in HL [Willems, 2004; Mencia et al., 2009; Mahdieh et al., 2010a]. *GJB2* mutations are seen in 50% of autosomal recessive HL in the Caucasians [Kelsell et al., 1997; Tekin et al., 2001]. Some genes e.g. *GJB2* gene is expressed in a variety of organs of the body while others such as *OTOA*ncorin is only

Autosomal recessive non-syndromic HL (ARNSHL) was first described in 1846. It is the severest form of congenital HL in which there is a defect in cochlea in nearly all cases. Loci of ARNSHL are designated as the DFNB; DF stands for Deafness and B indicates the autosomal recessive pattern of inheritance. Up to date, 46 genes and nearly 100 loci have been identified for HL (Table 3). Regarding different studies, connexin 26 gene mutations differ depending on geographical place and ethnicity [Zelante et al., 1997; Morell et al., 1998; Mahdieh & Rabbani, 2009]. Here, we discuss the most common genes causing

The first locus of ARNSHL designated as DFNB1 was identified by Guilford and colleagues in 1994. These researches confirmed linkage to chromosome 13q12-q13 in two consanguineous families [Guilford et al., 1994]. More consanguineous families of different ethnic groups were linked to the DFNB1 locus [Morle et al., 2000]. Phenotypic differences were observed within different families which indicated that allelic heterogeneity may be

*GJB2* is a small gene encompassing 5.5 Kb. It has two exons encoding a 4.2Kb mRNA and a protein of 226 amino acids. A six repeat of G is located at position 30 to 35 of coding region of *GJB2* gene from which deletion of one G is known as 35delG or 30delG (Figure 1) [Kelley et al., 1998]. 35delG is the most common mutation in the Caucasians and may cause up to 70% of all *GJB2* gene mutations. Profound HL caused by *GJB2* gene mutations is found in 50% of the cases; 30% are severe, 20% moderate and 1-2% are mild cases [Smith & Hone, 2003]. Other *GJB2* mutations have been reported with higher frequencies in some ethnic

non-syndromic HL. Different patterns of inheritance have been observed in NSHL.

nonsyndromic HL (http://hereditaryhearingloss.org).

**4. Non-syndromic HL** 

**4.1 Different types of NSHL** 

expressed in the inner ear.

present in the locus DFNB1.

ARNSHL.

**4.1.1 Autosomal recessive non-syndromic HL** 

**4.1.1.1** *GJB2* **and** *GJB6* **genes and connexins** 
