GM09459

GM09459 LCL from B-Lymphocyte

Description:

USHER SYNDROME, TYPE IC; USH1C
USH1C GENE; USH1C

Affected:

No Data

Sex:

Male

Age:

44 YR (At Sampling)

Overview

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

Relation to Proband

father

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Clinically unaffected; Acadian; 1 affected son (GM09458); donor subject is heteroygous 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

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

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.

Phenotypic Data

Remarks

Publications

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

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

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