GM20383

GM20383 LCL from B-Lymphocyte

Description:

CEROID LIPOFUSCINOSIS, NEURONAL 3, JUVENILE; CLN3
CLN3 GENE; CLN3

Affected:

Yes

Sex:

Female

Age:

30 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Class

Disorders of the Nervous System

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; vision loss at age 5 years; seizures at age 11 years; movement and intelligence declined at age 12 years; EM showed fingerprint profile; donor subject is a compound heterozygote: one allele has a 1.02 kb deletion including 217 bp of the open reading frame (nucleotides 598-814), corresponding to 2 exons resulting in a frameshift that generates a termination codon 84 bp downstream of the deletion junction [1-KB DEL, NT598] and a second allele has a G>A transition at nucleotide 1020 in exon 11 of the CLN3 gene [1020G>A] resulting in a substitution of lysine for glutamic acid at codon 295 [Glu295Lys (E295K)].

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin confirmed by LINE assay

Gene

CLN3

Chromosomal Location

16p12.1

Allelic Variant 1

204200.0001; BATTEN DISEASE

Identified Mutation

1-KB DEL, NT598; The International Batten Disease Consortium (1995) demonstrated that the mutation responsible for 73% of Batten disease chromosomes as identified by the 56 haplotype is a genomic deletion of 1.02 kb, including 217 bp of the open reading frame (nucleotides 598-814), corresponding to 2 exons. Deletion of these 217 bp of coding sequence produces a frameshift, generating a TAA termination codon 84 bp downstream of the deletion junction. The predicted translation product is a truncated protein of 181 amino acids consisting of the first 153 residues of the protein, followed by 28 novel amino acids before the stop codon. Even more of the patients in Finland carry the 1.02-kb deletion, namely 90%. Jarvela et al. (1996) developed a rapid diagnostic solid-phase minisequencing test to detect this deletion.

Gene

CLN3

Chromosomal Location

16p12.1

Allelic Variant 2

204200.0005; BATTEN DISEASE, PROTRACTED

Identified Mutation

GLU295LYS; Wisniewski et al. (1998) described compound heterozygosity for CLN3 mutations in 2 sibs with the rare, protracted form of juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten disease. Both carried the 1.02-kb CLN3 deletion (204200.0001) on 1 CLN3 allele and had a G-to-A missense mutation at nucleotide 1020 on the other allele, which predicted a glu295-to-lys amino acid substitution. The sister died at age 51 of aspiration pneumonia; the brother was living at age 39. The sister had progressive visual loss, beginning at 5 years of age, and became totally blind at age 13. From 45 years of age, she had progressive impairment of coordination, memory loss, problems with naming and calculation, and episodes of confusion. A general examination at age 48 was normal. Neurologic examination showed disorientation for time and space, impairment of short- and long-term memory, dysarthria, oromandibular dystonia, and naming deficit. A pendular nystagmus was present. The optic fundi showed optic nerve atrophy, pigmentary retinal degeneration, and spicules. The brother began to lose vision at age 5 years, leading to blindness at the age of 12. The main finding on examination was blindness secondary to optic atrophy and pigmentary retinal degeneration.

Phenotypic Data

Remarks

Publications

Zhong N, Wisniewski KE, Kaczmarski AL, Ju W, Xu WM, Xu WW, Mclendon L, Liu B, Kaczmarski W, Sklower Brooks SS, Brown WT, Molecular screening of Batten disease: identification of a missense mutation (E295K) in the CLN3 gene. Hum Genet102(1):57-62 1998

PubMed ID: 9490299