[Frontiers in Bioscience E4, 924-933, January 1, 2012]

Nonsyndromic X-linked hearing loss

Mee Hyun Song1, Kyu-Yup Lee2, Jae Young Choi3, Jinwoong Bok4, Un-Kyung Kim5

1Department of Otorhinolaryngology, Kwandong University College of Medicine, Goyang, South Korea, 2Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Kyungpook National University, Daegu, South Korea 3Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea, 4Department of Anatomy, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea, 5Department of Biology, Kyungpook National University, Daegu, South Korea

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Classification
4. Clinical characteristics and molecular genetics
4.1. DFNX1 (DFN2)
4.2. DFNX2 (DFN3)
4.3. DFNX3 (DFN4)
4.4. DFNX4 (DFN6)
4.5. DFNX5 (AUNX1)
5. Structural and functional analysis of mutations in the causative genes
5.1. DFNX1 (DFN2) - PRPS1
5.2. DFNX2 (DFN3) - POU3F4
6. Developmental pathogenesis
6.1. DFNX1 (DFN2)
6.2. DFNX2 (DFN3)
7. Summary and perspective
8. Acknowledgement
9. References

1. ABSTRACT

To date, 135 loci and 50 genes have been identified as causes of nonsyndromic hearing loss. Until recently, four loci (DFN2, DFN3, DFN4, and DFN6) had been implicated in nonsyndromic X-linked hearing loss; however, a new classification (DFNX1-5) has been proposed to reduce confusion in the terminology. The different types of nonsyndromic X-linked hearing loss demonstrate various clinical features in terms of the onset and progressiveness of hearing loss, pattern of audiogram, and the presence or absence of inner ear malformations. In addition to the POU3F4 gene, which was the first gene identified as causing nonsyndromic X-linked hearing loss, a second gene, PRPS1, has recently been identified to be the causative gene of DFNX1 (DFN2). This study reviews the new classification system, as well as the clinical features, molecular genetics, and developmental pathogenesis of different forms of nonsyndromic X-linked hearing loss.