GM09458
LCL from B-Lymphocyte
Description:
USHER SYNDROME, TYPE IC; USH1C
USH1C GENE; USH1C
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Ophthalmologic Disorders |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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LCL from B-Lymphocyte
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Race
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White
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Ethnicity
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ACADIAN
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| Gene |
USH1C |
| Chromosomal Location |
11p15.1 |
| Allelic Variant 1 |
605242.0004; USHER SYNDROME, TYPE 1C |
| Identified Mutation |
216G>A; In cell lines from an Acadian family with Usher syndrome IC (276904), Bitner-Glindzicz et al. (Nat Genet 26:56-60, 2000) found a homozygous G-to-A change at position 216 of the USH1C cDNA in the affected individual. The substitution did not change an amino acid and examination suggested the creation of a new splice site. Analysis of USH1C lymphoblastoid cDNA from the affected individual showed 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. (Hum Genet 110:95-97, 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, designated 9VNTR(t,t), 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 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.
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| Gene |
USH1C |
| Chromosomal Location |
11p15.1 |
| Allelic Variant 2 |
605242.0004; USHER SYNDROME, TYPE 1C |
| Identified Mutation |
216G>A; In cell lines from an Acadian family with Usher syndrome IC (276904), Bitner-Glindzicz et al. (Nat Genet 26:56-60, 2000) found a homozygous G-to-A change at position 216 of the USH1C cDNA in the affected individual. The substitution did not change an amino acid and examination suggested the creation of a new splice site. Analysis of USH1C lymphoblastoid cDNA from the affected individual showed 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. (Hum Genet 110:95-97, 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, designated 9VNTR(t,t), 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 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.
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| Remarks |
Clinically affected; Acadian; hearing loss noted at age 6 months; profound bilateral sensorineural hearing loss confirmed via audiometric tests; funduscopic exam shows pale optic discs, attenuated retinal vessels, and mild bone spicule pigmentary changes in the midperipheral retina; speech awareness threshold is 105dB for left ear with no response at maximum intensity for right ear; donor subject is homozygous for a G>A transition at nucleotide 216 in exon 3 of the USH1C gene [216G>A] resulting in a splice-site mutation that causes a 35 bp frame-shift deletion (new splice site is created that eliminates the use of the normal splice site resulting in loss of normal mRNA)
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| Lentz J, Savas S, Ng SS, Athas G, Deininger P, Keats B, The USH1C 216G-->A splice-site mutation results in a 35-base-pair deletion Human genetics116:225-7 2004 |
| PubMed ID: 15578223 |
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| Bitner-Glindzicz M, Lindley KJ, Rutland P, Blaydon D, Smith VV, Milla PJ,
Hussain K, Furth-Lavi J, Cosgrove KE, Shepherd RM, Barnes PD, O'Brien RE,
Farndon PA, Sowden J, Liu XZ, Scanlan MJ, Malcolm S, Dunne MJ, Aynsley-Green A,
Glaser B, A recessive contiguous gene deletion causing infantile hyperinsulinism,
enteropathy and deafness identifies the Usher type 1C gene. Nat Genet26(1):56-60 2000 |
| PubMed ID: 10973248 |
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| Pelias MZ, Lemoine DR, Kossar AL, Ward LJ, Wilson AF, Elston RC, Linkage studies of Usher syndrome: analysis of an Acadian kindred in Louisiana. Cytogenet Cell Genet47:111-2 1988 |
| PubMed ID: 3162715 |
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| Kloepfer HW, Laguaite JK, The hereditary syndrome of congenital deafness and retinitis pigmentosa. (Usher's syndrome). Laryngoscope76:850-62 1966 |
| PubMed ID: 5937908 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Medium |
Roswell Park Memorial Institute Medium 1640 with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not Inactivated |
| Substrate |
None specified |
| Subcultivation Method |
dilution - add fresh medium |
| Supplement |
- |
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