NA09404
DNA from Fibroblast
Description:
CEROID LIPOFUSCINOSIS, NEURONAL 2, LATE INFANTILE TYPE; CLN2
CLN2 GENE; CLN2
|
Repository
|
NIGMS Human Genetic Cell Repository
|
| Subcollection |
Heritable Diseases
Lysosomal Storage Diseases
Pharmacogenetics |
| Class |
Disorders of the Nervous System |
| Quantity |
50 µg |
| Quantitation Method |
Please see our FAQ |
|
Cell Type
|
Fibroblast
|
|
Transformant
|
Untransformed
|
|
Sample Source
|
DNA from Fibroblast
|
|
Race
|
Asian
|
|
Relation to Proband
|
proband
|
|
Confirmation
|
Clinical summary/Case history
|
|
Species
|
Homo sapiens
|
|
Common Name
|
Human
|
|
Remarks
|
|
| Passage Frozen |
14 |
| |
| 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 |
I287N; CEROID LIPOFUSCINOSIS, NEURONAL 2 |
| Identified Mutation |
ILE287ASN |
| |
| Gene |
CYP2D6 |
| Chromosomal Location |
22q13.1 |
| Allelic Variant 1 |
124030.0005; DEBRISOQUINE, POOR METABOLISM OF |
| Identified Mutation |
PRO34SER; This allelic variant is also known as CYP2D6*10 or CYP2D6(J) or CYP2D6(Ch1, Ch2). Kagimoto et al. (J Biol Chem 265:17209-17214, 1990) identified a 188C-T transition in exon 1 of the CYP2D6 gene, resulting in a pro34-to-ser (P34S) substitution as a cause of the debrisoquine poor metabolizer phenotype (608902). |
| |
| Gene |
CYP2D6 |
| Chromosomal Location |
22q13.1 |
| Allelic Variant 2 |
124030.0005; DEBRISOQUINE, POOR METABOLISM OF |
| Identified Mutation |
PRO34SER; This allelic variant is also known as CYP2D6*10 or CYP2D6(J) or CYP2D6(Ch1, Ch2). Kagimoto et al. (J Biol Chem 265:17209-17214, 1990) identified a 188C-T transition in exon 1 of the CYP2D6 gene, resulting in a pro34-to-ser (P34S) substitution as a cause of the debrisoquine poor metabolizer phenotype (608902). |
| Remarks |
Seizures, myoclonus, dementia, and spasticity; a brother died at age 11 with the same disease; diagnosis is most consistent with late infantile amaurotic idiocy; slightly elevated urinary dolichol; CLN2 protease deficient; the donor subject has one allele which carries a T-to-A transition at nucleotide g.4023 (c.860T>A) which converts the ile-287 codon (ATC) to asn (AAC), resulting in a missense mutation in exon 7 of the CLN2 (TPP1) gene [Ile287Asn (I287N)]. |
| Vidal-Donet JM, Cárcel-Trullols J, Casanova B, Aguado C, Knecht E, Alterations in ROS Activity and Lysosomal pH Account for Distinct Patterns of Macroautophagy in LINCL and JNCL Fibroblasts PloS one8:e55526 2012 |
| PubMed ID: 23408996 |
| |
| Jennings JJ, Zhu JH, Rbaibi Y, Luo X, Chu CT, Kiselyov K, Mitochondrial aberrations in mucolipidosis Type IV The Journal of biological chemistry281:39041-50 2006 |
| PubMed ID: 17056595 |
| |
| Soyombo AA, Tjon-Kon-Sang S, Rbaibi Y, Bashllari E, Bisceglia J, Muallem S, Kiselyov K, TRP-ML1 regulates lysosomal pH and acidic lysosomal lipid hydrolytic activity The Journal of biological chemistry281:7294-301 2005 |
| PubMed ID: 16361256 |
| |
| 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 |
| |
| Sohar I, Sleat DE, Jadot M, Lobel P, Biochemical characterization of a lysosomal protease deficient in classical late infantile neuronal ceroid lipofuscinosis (LINCL) and development of an enzyme-based assay for diagnosis and exclusion of LINCL in human specimens and animal models. J Neurochem73:700-11 1999 |
| PubMed ID: 10428067 |
|
|