GM10354
LCL from B-Lymphocyte
Description:
USHER SYNDROME, TYPE IC; USH1C
USH1C GENE; USH1C
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| Subcollection |
Heritable Diseases |
| Class |
Ophthalmologic Disorders |
|
Biopsy Source
|
Peripheral vein
|
|
Cell Type
|
B-Lymphocyte
|
|
Tissue Type
|
Blood
|
|
Transformant
|
Epstein-Barr Virus
|
|
Sample Source
|
LCL from B-Lymphocyte
|
|
Race
|
White
|
|
Ethnicity
|
ACADIAN
|
|
Family Member
|
1
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Clinical summary/Case history
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
| |
| GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME |
PCR analysis of DNA from this cell culture gave a positive result with a primer for Yq11, DYS227. |
| |
| 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.
|
| |
| 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.
|
| Remarks |
Clinically affected; Acadian; 2 similarly affected sibs; vascular and pigmentary changes typical of RP; visual field defect; retinal abnormality; visual acuity without glasses is 20/25 in right eye and 20/30 in left at distant points; 113dB+ hearing loss for right ear and 116dB+ loss for left; poor manual and oral commun skill; profound bilateral sensorineural hearing loss; absent reflex thresholds for both ears; 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)
|
| 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 |
| |
| DeAngelis MM, Doucet JP, Drury S, Sherry ST, Robichaux MB, Den Z, Pelias MZ, Ditta GM, Keats BJ, Deininger PL, Batzer MA, Assembly of a high-resolution map of the Acadian Usher syndrome region and localization of the nuclear EF-hand acidic gene Biochimica et biophysica acta1407:84-91 1998 |
| PubMed ID: 9639681 |
| |
| Smith RJ, Lee EC, Kimberling WJ, Daiger SP, Pelias MZ, Keats BJ, Jay M, Bird A, Reardon W, Guest M, et al, Localization of two genes for Usher syndrome type I to chromosome 11. Genomics14:995-1002 1992 |
| PubMed ID: 1478678 |
| |
| Smith RJ, Pelias MZ, Daiger SP, Keats B, Kimberling W, Hejtmancik JF, Clinical variability and genetic heterogeneity within the Acadian Usher population. Am J Med Genet43:964-9 1992 |
| PubMed ID: 1415347 |
| |
| 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 |
| |
| 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 |
- |
|