Usher syndrome

Usher syndrome (USH) is characterized by hearing impairment, progressive vision loss due to retinitis pigmentosa (RP) and, in some cases, by vestibular dysfunction. It is inherited as an autosomal recessive trait and is the most frequent cause of combined deaf-blindness in humans.

One of the earliest descriptions of this syndrome was given by Dr Albrecht von Graefe who identified the disease among Jewish people in Berlin in 1858. The disease was later named after Dr Charles Usher, a Scottish ophthalmologist who described in 1914 the hereditary nature of the disorder in 19 cases out of 69 patients with retinitis pigmentosa.

Usher syndrome is clinically and genetically heterogeneous. Though the disease is defined by congenital bilateral deafness and a later onset of visual field loss, symptoms vary from person to person and progress at different rates. Balance may also be affected. At least 12 chromosomal loci have been identified so far and assigned to three major clinical types: USH1, USH2 and USH3. Depending on the causative genes, USH1 is further divided into distinct subtypes, designated as types 1B through 1H ( see Table 1). Three genes have been assigned to USH2 (corresponding to three genetic subtypes USH2A, C, D respectively). Recently, a role of PDZD7 as either contributor to digenic disease or modifier of retinal disease expression in Usher syndrome has been suggested. USH3 has at least two genetic forms, but only one causative gene has been identified so far.

Table 1: Usher syndrome subtypes, genes and proteins
Subtype Gene locus Gene symbol Protein name Protein function/possible function
Usher 1A Withdrawn
Usher 1B 11q13.5 MYO7A Myosin VIIa Actin-based motor protein
Usher 1C 11q15.1 USH1C Harmonin PDZ-domain containing protein
Usher 1D 10q21-q22 CDH23 Cadherin-23 Integral membrane adhesion protein
Usher 1E 21q21 Unknown Unknown Unknown
Usher 1F 10q21.1 PCDH15 Protocadherin15 Integral membrane adhesion protein
Usher 1G 17q24-25 USH1/SANS Sans Putative scaffold protein
Usher 1H 15q22-23 Unknown Unknown Unknown
Usher 2A 1q41 USH2A Usherin Integral membrane protein
Usher 2B Withdrawn
Usher 2C 5q14.3-21.3 VLGR1 (also known as GPR98) Vlgr1 G-protein coupled receptor
Usher 2D 9q32-q34 WHRN (also know as DFNB31) Whirlin PDZ-domain containing protein
Usher 3A 3q21-q25 USA3A Clarin 1 Integral membrane protein
Usher 3B 20q Unknown Unknown Unknown