GM00378

GM00378 Fibroblast

Description:

CYSTINOSIS, LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE
CYSTINOSIN; CTNS

Affected:

Yes

Sex:

Female

Age:

7 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Class

Disorders of Amino Acid Metabolism

Cell Type

Fibroblast

Transformant

Untransformed

Race

White

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Conjunctiva and cornea contain typical cystinotic crystals; elevated white cell 1/2 cystine concentration; normal renal function at age 10, but by age 13 developed renal glomerular insufficiency; similarly affected brother; results from next generation sequencing using human genome version hg19 confirmed by Sanger sequencing indicated that donor subject has compound heterozygous mutations in the CTNS gene: allele 1 has a splice site mutation at the +2 position of exon 11 [IVS11+2 T>C] or c.970+2T>C resulting in the skipping of exon 11 (inherited from mother, GM00907) and allele 2 has a G>A transition at nucleotide 753 in exon 7 [753G>A] resulting in a substitution of a termination codon for tryptophan at codon 138 [Trp138Ter (W138X)] or p.W138*/c.414G>A (inherited from father, GM00906), Zykovich et al. Molecular Genetics and Metabolism Reports 5 (2015) 63-66.

Characterizations

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

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

Gene

CTNS

Chromosomal Location

17p13

Allelic Variant 1

exon 11 skipped; CYSTINOSIS, LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE

Identified Mutation

IVS11+2,T>C

Gene

CTNS

Chromosomal Location

17p13

Allelic Variant 2

606272.0003; CYSTINOSIS, LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE

Identified Mutation

TRP138TER, 414G>A; One family from Northern Ireland and one from Eire were found by Town et al. (1998) to have the same mutation as the basis of nephropathic cystinosis (219800): a TGG-to-TGA transition at nucleotide 753 resulting in a trp138-to-ter (W138X) nonsense mutation.

Phenotypic Data

Remarks

Publications

Zykovich A, Kinkade R, Royal G, Zankel T, Molecular genetics and metabolism reports5:63-66 2015

PubMed ID: 28649545

Helip-Wooley A, Park MA, Lemons RM, Thoene JG, Expression of CTNS alleles: subcellular localization and aminoglycoside correction in vitro. Mol Genet Metab75(2):128-33 2002

PubMed ID: 11855931

Langman CB, Moore ES, Thoene JG, Schneider JA, Renal failure in a sibship with late-onset cystinosis. J Pediatr107:755-6 1985

PubMed ID: 4056976