GM16485

GM16485 Fibroblast from Skin, Unspecified

Description:

CEROID LIPOFUSCINOSIS, NEURONAL 2, LATE INFANTILE TYPE; CLN2
CLN2 GENE; CLN2

Affected:

Yes

Sex:

Female

Age:

No Data

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Class

Disorders of the Nervous System

Biopsy Source

Unspecified

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Sample Source

Fibroblast from Skin, Unspecified

Race

Not Reported

Ethnicity

Hispanic/Latino

Family Member

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

CABM011; clinically affected; seizures at 3 years of age, vision deterioration and cognitive dysfunction at 4 years of age; motor coordination dysfunction; CLN2 protease deficient; donor subject is a compound heterozygote: one allele carries a C-to-T transition at nucleotide g.3084 (c.379C>T) which converts the arg-127 codon (CGA) to a stop codon (TGA), resulting in a nonsense mutation in exon 4 of the CLN2 (TPP1) gene [ARG127TER (R127X)] and a second allele carries a C-to-T transition at nucleotide g.3670 (c.622C>T) which converts the arg-208 codon (CGA) to a stop codon (TGA), resulting in a nonsense mutation in exon 6 of the CLN2 (TPP1) gene [ARG208TER (R208X)]; same subject as GM27465 (iPSC).

Characterizations

PDL at Freeze

5.42

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

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

Gene

CLN2

Chromosomal Location

11p15.5

Allelic Variant 1

R127X; CEROID LIPOFUSCINOSIS, NEURONAL 2

Identified Mutation

ARG127TER

Gene

CLN2

Chromosomal Location

11p15.5

Allelic Variant 2

607998.0003; CEROID LIPOFUSCINOSIS, NEURONAL 2

Identified Mutation

ARG208TER; In two sibs with late-infantile neuronal ceroid lipofuscinosis (LINCL), Sleat et al. [Science 277: 1802-1805, (1997)] found compound heterozygosity for a C-to-T transition that resulted in the conversion of codon 208 (CGA) to a stop codon (TGA). In the other allele, the conserved AG of the intronic 3-prime splice junction sequence was changed to AC, which was predicted to result in intron splicing (204500.0004). Each parent possessed a single different mutant allele.

Phenotypic Data

Remarks

Publications

Baradaran-Heravi A, Balgi AD, Hosseini-Farahabadi S, Choi K, Has C, Roberge M, Effect of small molecule eRF3 degraders on premature termination codon readthrough Nucleic acids research49:3692-3708 2021

PubMed ID: 33764477

Sima N, Li R, Huang W, Xu M, Beers J, Zou J, Titus S, Ottinger EA, Marugan JJ, Xie X, Zheng W, Neural stem cells for disease modeling and evaluation of therapeutics for infantile (CLN1/PPT1) and late infantile (CLN2/TPP1) neuronal ceroid lipofuscinoses Orphanet journal of rare diseases13:54 2017

PubMed ID: 29631617

Xu M, Liu K, Swaroop M, Sun W, Dehdashti SJ, McKew JC, Zheng W, A phenotypic compound screening assay for lysosomal storage diseases Journal of biomolecular screening19:168-75 2013

PubMed ID: 23983233

Xu M1, Liu K, Swaroop M, Porter FD, Sidhu R, Firnkes S, Ory DS, Marugan JJ, Xiao J, Southall N, Pavan WJ, Davidson C, Walkley SU, Remaley AT, Baxa U, Sun W, McKew JC, Austin CP, Zheng W., δ-Tocopherol reduces lipid accumulation in Niemann-Pick type C1 and Wolman cholesterol storage disorders. J Biol Chem287(47):39349-60 2012

PubMed ID: 23035117

Sleat DE, Gin RM, Sohar I, Wisniewski K, Sklower-Brooks S, Pullarkat RK, Palmer DN, Lerner TJ, Boustany RM, Uldall P, Siakotos AN, Donnelly RJ, Lobel P, Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder. Am J Hum Genet64(6):1511-23 1999

PubMed ID: 10330339