NA00059
DNA from Fibroblast
Description:
CANAVAN DISEASE
ASPARTOACYLASE; ASPA
HEXOSAMINIDASE A; HEXA
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of the Nervous System |
| Quantity |
10 µg |
| Quantitation Method |
Please see our FAQ |
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Cell Type
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Fibroblast
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Tissue Type
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Skin
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Transformant
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Untransformed
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Sample Source
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DNA from Fibroblast
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Race
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Not Reported
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| PDL at Freeze |
6.58 |
| Passage Frozen |
10 |
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| aspartoacylase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.5.1.15 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME |
PCR analysis of DNA from this cell culture gave a negative result with a primer for Yq11, DYS227. |
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| N-ACETYLASPARTOACYLASE |
Dr Reuben Matalon (personal communication) has reported that this fibroblast culture shows N-acetylaspartoacylase activity which falls in the deficient range. |
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| Gene |
ASPA |
| Chromosomal Location |
17pter-p13 |
| Allelic Variant 1 |
608034.0003; CANAVAN DISEASE |
| Identified Mutation |
ALA305GLU; In patients with Canavan disease (271900), Kaul et al. (1994) identified a 914C-A change in exon 6 of the ASPA gene, resulting in an ala305-to-glu (A305E) substitution. The mutation was found exclusively in non-Jewish patients and constituted 60% of the 40 chromosomes analyzed. Expression of the mutation in COS-1 cells showed a complete loss of ASPA enzyme activity.
Shaag et al. (A J Hum Genet 57:572-580,1995) found the ala305-to-glu (A305E) mutation due to a GCA-to-GAA transversion in 15 out of 38 mutant alleles in 19 non-Jewish patients. This distribution was pan-European, suggesting that it is the most ancient mutation.
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| Gene |
ASPA |
| Chromosomal Location |
17pter-p13 |
| Allelic Variant 1 |
G176D; CANAVAN DISEASE |
| Identified Mutation |
GLY176ASP |
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| Gene |
ASPA |
| Chromosomal Location |
17pter-p13 |
| Allelic Variant 1 |
608034.0005; CANAVAN DISEASE |
| Identified Mutation |
TYR231TER; In Ashkenazi Jewish patients with Canavan disease, Kaul et al. [Genomics 21: 364-370 1994)] identified a 693C-A nonsense mutation in exon 5 of the ASPA gene (Y231X). Expression of the mutation in COS-1 cells showed a complete loss of ASPA enzyme activity. Among Ashkenazi Jewish patients with Canavan disease, Kaul et al. [Hum. Genet. 59: 95-102 (1996)] found that the G285A missense mutation (608034.0001) and the Y231X nonsense mutation accounted for 97% of 104 mutant chromosomes examined. |
| Remarks |
Clinically affected; skin fibroblasts show deficient N-acetylaspartoacylase activity; for the ASPA gene, the donor subject is heterozygous for a c.914 C>A (exon 6, A305E), heterozygous for a novel c.527 C>A mutation (exon 4, G176D), and heterozygous for a c.693 C>T polymorphism (exon 5, Y231X); donor subject is also homozygous for a R249W mutation in the HEXA gene (83/17 mut/wt), associated with HEX A pseudodeficiency; similarly affected sibling (GM00060). Same subject as GM28249 (iPSC). |
| Feng L, Chao J, Zhang M, Pacquing E, Hu W, Shi Y, Developing a human iPSC-derived three-dimensional myelin spheroid platform for modeling myelin diseases iScience26:108037 2023 |
| PubMed ID: 37867939 |
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| Chao J, Feng L, Ye P, Chen X, Cui Q, Sun G, Zhou T, Tian E, Li W, Hu W, Riggs AD, Matalon R, Shi Y, Therapeutic development for Canavan disease using patient iPSCs introduced with the wild-type iScience25:104391 2020 |
| PubMed ID: 35637731 |
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| Feng L, Chao J, Tian E, Li L, Ye P, Zhang M, Chen X, Cui Q, Sun G, Zhou T, Felix G, Qin Y, Li W, Meza ED, Klein J, Ghoda L, Hu W, Luo Y, Dang W, Hsu D, Gold J, Goldman SA, Matalon R, Shi Y, Cell-Based Therapy for Canavan Disease Using Human iPSC-Derived NPCs and OPCs Advanced science (Weinheim, Baden-Wurttemberg, Germany)7:2002155 2020 |
| PubMed ID: 33304759 |
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| Kalman L, Wilson JA, Buller A, Dixon J, Edelmann L, Geller L, Highsmith WE, Holtegaard L, Kornreich R, Rohlfs EM, Payeur TL, Sellers T, Toji L, Muralidharan K, Development of genomic DNA reference materials for genetic testing of disorders common in people of ashkenazi jewish descent The Journal of molecular diagnostics : JMD11:530-6 2009 |
| PubMed ID: 19815695 |
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