| Full gene name: | Usher syndrome 1C (autosomal recessive, severe) |
|---|---|
| Entrez Gene ID: | 10083 |
| Location: | 11p14.3 |
| Synonyms: | ush1cpst, PDZ-73, PDZ-45, PDZ-73/NY-CO-38, DFNB18, NY-CO-38, NY-CO-37, PDZ73, AIE-75 |
| Type: | protein-coding |
SNPs given by the user that are near or inside this gene:
| SNP | Distance (bp) | Direction |
|---|---|---|
| rs5215 | 106812 | downstream |
This gene encodes a scaffold protein that functions in the assembly of Usher protein complexes. The protein contains PDZ domains, a coiled-coil region with a bipartite nuclear localization signal and a PEST degradation sequence. Defects in this gene are the cause of Usher syndrome type 1C and non-syndromic sensorineural deafness autosomal recessive type 18. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
| OMIM ID: | `OMIM ID 605242 `_ |
|---|
Allelic Variants (Selected Examples)
.0001 USHER SYNDROME, TYPE IC
In patients with Usher syndrome IC (276904) in a consanguineous Lebanese family (Saouda et al., 1998), Verpy et al. (2000) identified deletion of 1 nucleotide at the intron 5/exon 6 junction of the USH1C gene. This mutation (IVS5-2delA) affected the invariant A of the acceptor splice site AG dinucleotide and was therefore expected to lead to aberrant splicing, such as a skipping of the 25-bp exon 6, creating a premature stop codon in exon 8. The same mutation was found in homozygous state in 8 Usher syndrome type I affected children from an unrelated Lebanese family.
.0002 USHER SYNDROME, TYPE IC
In a consanguineous Muslim family living in England with Usher syndrome IC (276904) with 3 affected children, Verpy et al. (2000) found insertion of a C within a stretch of 6 consecutive cytosines (nucleotide positions 233-238) in exon 3 of the USH1C gene. This insertion (238-239insC) was expected to result in translation of 68 out-of-frame amino acids and protein termination at codon 148 in exon 5. Verpy et al. (2000) found the same 238-239insC mutation in 4 patients from Germany (all of European descent) with Usher syndrome but no detected mutations of MYO7A (276903). Bitner-Glindzicz et al. (2000) likewise found this insertion in a Pakistani family.
Zwaenepoel et al. (2001) found that all carriers of the 238-239insC mutation share a common haplotype. A different common haplotype was found in 2 carriers of the IVS1+1G-T mutation (605242.0005). Zwaenepoel et al. (2001) proposed a founder effect of these 2 mutations.
.0003 USHER SYNDROME, TYPE IC
In Louisiana-Acadian patients with Usher syndrome IC (276904), Verpy et al. (2000) found no mutation in the coding sequence of the harmonin gene; however, they detected an expansion of a variable number of tandem repeats (VNTR) of a 45-bp element in intron 5 of the USH1C gene. They detected no control individuals with 2 alleles bearing more than 6 repeats. In all but 1 of 11 Acadian patients, they found an allele with 9 tandem repeats in the homozygous state. These 10 individuals were from 7 families. The remaining Acadian patient carried the 9 tandem repeats on 1 chromosome and the 238-239insC mutation (605242.0002) on the other. Verpy et al. (2000) proposed that this 405-bp intronic sequence composed of 9 tandem repeats was responsible for the disease in the Acadian population of Louisiana. The repeat expansion was predicted to inhibit transcription, as shown for the expanded GAA triplet repeats from intron 1 of the Friedreich ataxia gene (229300). Alternatively, it may cause abnormal posttranscriptional processing.
See 605242.0004 and Savas et al. (2002).
.0004 USHER SYNDROME, TYPE IC
In cell lines from an Acadian family with Usher syndrome IC (276904), Bitner-Glindzicz et al. (2000) found a G-to-A change at position 216 of the USH1C cDNA. The affected individual was homozygous for the substitution and the parents were heterozygous. Although this substitution did not change an amino acid, examination of the sequence suggested that it might create a new splice site. Analysis of USH1C lymphoblastoid cDNA from the Acadian family showed that the affected individual produced a shortened RT-PCR product. Sequencing revealed a 39-bp deletion, consistent with the creation of a new splice site within exon 3.
Savas et al. (2002) found that 43 of 44 Acadian patients with Usher syndrome were homozygous for both the 216G-A mutation and for the 45-bp VNTR polymorphism in intron 5 (605242.0003) of the USH1C gene. The remaining Acadian patient was a compound heterozygote for the 216G-A allele (with the intron 5 VNTR in cis) and 238-239insC (605242.0002), an USH1C mutation found in other populations. The findings demonstrated that the VNTR polymorphism, designated 9VNTR(t,t), had complete linkage disequilibrium with the 216G-A mutation in the Acadian population. Among 82 Acadian controls, 1 was heterozygous for 216G-A/9VNTR(t,t). The 238-239insC mutation was not found in Acadian controls.
.0005 USHER SYNDROME, TYPE IC
A complete USH1C mutation screen in 4 carriers of the 238-239insC mutation (605242.0002) resulted in the detection of the second mutation in all of the carriers, and the identification of 3 novel mutations of which 2 were splice site mutations (IVS1+1G-T; IVS5+1G-A, 605242.0006) and the other a nonsense mutation (R31X; 605242.0007).
Zwaenepoel et al. (2001) found that 2 carriers of the IVS1+1G-T mutation share a common haplotype. A different common haplotype was found in all carriers of the 238-239insC mutation. Zwaenepoel et al. (2001) proposed a founder effect of these 2 mutations.
.0006 USHER SYNDROME, TYPE IC
See 605242.0005 and Zwaenepoel et al. (2001).
In an extensive genetic study of 9 Usher syndrome genes in 172 patients with Usher syndrome due to various genetic defects, Le Quesne Stabej et al. (2012) found that mutations in the USH1C gene were the second most common defect, accounting for 14.9% of families. Four families carried the intron 5 splice site mutation (495+1G-A), and haplotype analysis indicated a founder effect.
.0007 USHER SYNDROME, TYPE IC
See 605242.0005 and Zwaenepoel et al. (2001).
.0008 DEAFNESS, AUTOSOMAL RECESSIVE 18
In an Indian family in which nonsyndromic recessive deafness DFNB18 (602092) had been mapped to the same region of 11p as USH1C, Ahmed et al. (2002) identified a leaky splice site mutation in the harmonin gene, a G-to-C transversion at the +5 position of intron 12. Although affected individuals were homozygous for the mutation, wildtype spliced mRNA having exons 11 and 12 as well as mRNA that skipped exon 12 were found.
.0009 DEAFNESS, AUTOSOMAL RECESSIVE 18
In 1 of 32 Chinese multiplex families with nonsyndromic recessive deafness without retinitis pigmentosa (602092), Ouyang et al. (2002) found a C-to-G transversion in the alternatively spliced exon D of the USH1C gene, predicting an arg608-to-pro (R608P) substitution in the proline-, serine-, and threonine-rich region of harmonin.
.0010 USHER SYNDROME, TYPE IC
In a U.K. patient with type I Usher syndrome (276904), Blaydon et al. (2003) identified a 388G-A transition in exon 5 of the USH1C gene, resulting in a val130-to-ile (V130I) mutation. No mutation was identified in the other allele.
No pathways found linked to this gene.
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