Abstract
Usher syndrome (USH) is a combination of a progressive pigmentary retinopathy, indistinguishable from retinitis pigmentosa, and some degree of sensorineural hearing loss. USH can be subdivided in Usher type I (USHI), type II (USHII) and type III (USHIII), all of which are inherited as autosomal recessive traits. The three subtypes are genetically heterogeneous, with six loci so far identified for USHI, three for USHII and only one for USHIII. Mutations in a novel gene, USH2A, encoding the protein usherin, have recently been shown to be associated with USHII. The gene encodes a protein with partial sequence homology to both laminin epidermal growth factor and fibronectin motifs. We analysed 35 British and one Pakistani Usher type II families with at least one affected member, for sequence changes in the 20 translated exons of the USH2A gene, using heteroduplex analysis and sequencing. Probable disease-causing mutations in USH2A were identified in 15 of 36 (41.7%) Usher II families. The most frequently encountered mutation (11/15 families or 11/18 mutated alleles) was del2299G in exon 13, resulting in a frameshift and premature stop codon. Other mutations include insertions and point mutations, of which two are previously unreported. Five different polymorphisms were also detected. Our results indicate that mutations in this gene are responsible for disease in a large proportion of British Usher type II patients. Moreover, if screening for mutations in USH2A is considered, it is sensible to screen for the del2299G mutation first.
| Original language | English |
|---|---|
| Pages (from-to) | 503-509 |
| Number of pages | 7 |
| Journal | Experimental Eye Research |
| Volume | 72 |
| Issue number | 5 |
| DOIs | |
| State | Published - 2001 |
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All Science Journal Classification (ASJC) codes
- Ophthalmology
- Sensory Systems
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Spectrum of mutations in USH2A in british patients with usher syndrome type II. / Leroy, B. P.; Aragon-Martin, J. A.; Weston, M. D.; Bessant, D. A R; Willis, C.; Webster, A. R.; Bird, A. C.; Kimberling, W. J.; Payne, A. M.; Weston, Michael.
In: Experimental Eye Research, Vol. 72, No. 5, 2001, p. 503-509.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Spectrum of mutations in USH2A in british patients with usher syndrome type II
AU - Leroy, B. P.
AU - Aragon-Martin, J. A.
AU - Weston, M. D.
AU - Bessant, D. A R
AU - Willis, C.
AU - Webster, A. R.
AU - Bird, A. C.
AU - Kimberling, W. J.
AU - Payne, A. M.
AU - Weston, Michael
PY - 2001
Y1 - 2001
N2 - Usher syndrome (USH) is a combination of a progressive pigmentary retinopathy, indistinguishable from retinitis pigmentosa, and some degree of sensorineural hearing loss. USH can be subdivided in Usher type I (USHI), type II (USHII) and type III (USHIII), all of which are inherited as autosomal recessive traits. The three subtypes are genetically heterogeneous, with six loci so far identified for USHI, three for USHII and only one for USHIII. Mutations in a novel gene, USH2A, encoding the protein usherin, have recently been shown to be associated with USHII. The gene encodes a protein with partial sequence homology to both laminin epidermal growth factor and fibronectin motifs. We analysed 35 British and one Pakistani Usher type II families with at least one affected member, for sequence changes in the 20 translated exons of the USH2A gene, using heteroduplex analysis and sequencing. Probable disease-causing mutations in USH2A were identified in 15 of 36 (41.7%) Usher II families. The most frequently encountered mutation (11/15 families or 11/18 mutated alleles) was del2299G in exon 13, resulting in a frameshift and premature stop codon. Other mutations include insertions and point mutations, of which two are previously unreported. Five different polymorphisms were also detected. Our results indicate that mutations in this gene are responsible for disease in a large proportion of British Usher type II patients. Moreover, if screening for mutations in USH2A is considered, it is sensible to screen for the del2299G mutation first.
AB - Usher syndrome (USH) is a combination of a progressive pigmentary retinopathy, indistinguishable from retinitis pigmentosa, and some degree of sensorineural hearing loss. USH can be subdivided in Usher type I (USHI), type II (USHII) and type III (USHIII), all of which are inherited as autosomal recessive traits. The three subtypes are genetically heterogeneous, with six loci so far identified for USHI, three for USHII and only one for USHIII. Mutations in a novel gene, USH2A, encoding the protein usherin, have recently been shown to be associated with USHII. The gene encodes a protein with partial sequence homology to both laminin epidermal growth factor and fibronectin motifs. We analysed 35 British and one Pakistani Usher type II families with at least one affected member, for sequence changes in the 20 translated exons of the USH2A gene, using heteroduplex analysis and sequencing. Probable disease-causing mutations in USH2A were identified in 15 of 36 (41.7%) Usher II families. The most frequently encountered mutation (11/15 families or 11/18 mutated alleles) was del2299G in exon 13, resulting in a frameshift and premature stop codon. Other mutations include insertions and point mutations, of which two are previously unreported. Five different polymorphisms were also detected. Our results indicate that mutations in this gene are responsible for disease in a large proportion of British Usher type II patients. Moreover, if screening for mutations in USH2A is considered, it is sensible to screen for the del2299G mutation first.
UR - http://www.scopus.com/inward/record.url?scp=0034740617&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034740617&partnerID=8YFLogxK
U2 - 10.1006/exer.2000.0978
DO - 10.1006/exer.2000.0978
M3 - Article
C2 - 11311042
AN - SCOPUS:0034740617
VL - 72
SP - 503
EP - 509
JO - Experimental Eye Research
JF - Experimental Eye Research
SN - 0014-4835
IS - 5
ER -