Description:
SANDHOFF DISEASE
HEXOSAMINIDASE B; HEXB
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Lysosomal Storage Diseases |
| Class |
Disorders of Lipid Metabolism |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Race
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White
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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 |
5.19 |
| Passage Frozen |
5 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis |
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| MUTATION VERIFICATION |
Nakano and Suzuki (J Biol Chem 264:5155-5158 1989) reported the sequence analysis of a cDNA clone isolated from the fibroblasts of this Sandhoff disease patient. They found an extra 24 base segment between exons 12 and 13. This segment was identified as the 3 prime terminus of intron 12. The remainder of the coding sequence was completely normal. This insertion is inframe and adds 8 amino acids between amino acids 491 and 492 of the primary sequence of the normal B-hexosaminidase B chain protein. The finding is consistent with the slightly larger than normal size of the B subunit precursor protein observed by immunoprecipitation. No normally spliced mRNA was detected. Gene amplification and subsequent sequencing of genomic DNA indicated that the patient was a compound heterozygote. In one allele there was a single nucleotide transition from normal G to A at 26 bases from the 3 prime terminus of intron 12. This mutation generates a consensus sethe abnormal mRNAs that retain 24 bases of the 3 prime terminus of intron 12. The intron 12 and flanking exons 12 and 13 sequences were normal in the other allele. The authors believe that the other mutant allele is therefore likely to be of an mRNA-negative type. |
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| beta-N-acetylhexosaminidase (hexosaminidase A) |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.52; 3% activity. |
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| beta-N-acetylhexosaminidase (hexosaminidase B) |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.2.1.52 |
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| Gene |
HEXB |
| Chromosomal Location |
5q13 |
| Allelic Variant 1 |
268800.0002; SANDHOFF DISEASE, JUVENILE TYPE |
| Identified Mutation |
24-BP INS; In a case of the juvenile form reported by Wood and MacDougall (1976), Nakano and Suzuki (1989) showed that a cDNA clone isolated from fibroblasts contained an extra 24-base segment between exons 12 and 13. This segment was identified as the 3-prime terminus of intron 12. The remainder of the coding sequence was completely normal. The insertion was 'in frame' and added 8 amino acids between amino acids 491 and 492 of the enzyme protein. It was located only 5 amino acids away from a possible glycosylation site. Gene amplification by the PCR and subsequent sequencing of genomic DNA showed that the patient was a compound heterozygote. In 1 allele there was a single nucleotide transition from normal G to A at 26 bases from the 3-prime terminus of intron 12. This mutation generated a consensus sequence for the 3-prime splice site for an intron and thus explained the abnormal mRNAs that retain 24 bases of the 3-prime terminus of intron 12. The intron 12 and flanking exons 12 and 13 sequences were normal in the other allele. The other mutant allele was thought to be of an mRNA-negative type. The same mutation was found in a 35-year-old Japanese man with manifestations of juvenile Sandhoff disease: progressive neurogenic muscular atrophy, cerebellar ataxia, and mental deterioration beginning at age 10. Dlott et al. (1990) found the same mutation in cells from 2 juvenile Sandhoff disease patients and a third, asymptomatic individual.
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| Remarks |
Juvenile; cerebellar ataxia; severe mental retardation; deficient hexosaminidase A and B; same patient as GM02144; normal level of fibro preBchain mRNA; 3% of normal fibro Hex A activity; Hex B gene shows no gross abnormalities; point mutation in 1 beta-chain allele (c.1509-26G>A), resulting in an a 24-base insertion between exons 12 and 13 in cDNA. Mutation in the other allele is unknown. |
| Nakano T, Suzuki K, Genetic cause of a juvenile form of Sandhoff disease. Abnormal splicing of beta-hexosaminidase beta chain gene transcript due to a point mutation within intron 12. J Biol Chem264:5155-8 1989 |
| PubMed ID: 2522450 |
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| O'Dowd BF, Klavins MH, Willard HF, Gravel R, Lowden JA, Mahuran DJ, Molecular heterogeneity in the infantile and juvenile forms of Sandhoff disease (O-variant GM2 gangliosidosis). J Biol Chem261:12680-5 1986 |
| PubMed ID: 3017984 |
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| Hohmann P, Species- and cell-specific expression of H1 histones in tissue culture cells. Arch Biochem Biophys205:198-209 1980 |
| PubMed ID: 7447476 |
| dbSNP |
dbSNP ID: 15216 |
| NCBI GTR |
268800 SANDHOFF DISEASE |
| OMIM |
268800 SANDHOFF DISEASE |
| Omim Description |
GM2-GANGLIOSIDOSIS, TYPE II |
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HEXOSAMINIDASES A AND B DEFICIENCY; HEXB-HEXOSAMINIDASE B, INCLUDED; HEXB, INCLUDED |
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SANDHOFF DISEASE |
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SANDHOFF DISEASE, ADULT TYPE, INCLUDED |
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SANDHOFF DISEASE, INFANTILE TYPE, INCLUDED |
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SANDHOFF DISEASE, JUVENILE TYPE, INCLUDED |
| Passage Frozen |
5 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
3% |
| Medium |
Eagles Minimum Essential Medium with Earle's salts:Dulbecco's modified MEM with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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