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Usher 1A | Withdrawn | |||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Usher 2B | Withdrawn | |||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 |
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