NA04235
DNA from Fibroblast
Description:
HYPOPHOSPHATASIA, INFANTILE
ALKALINE PHOSPHATASE, LIVER; ALPL
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of Connective Tissue, Muscle, and Bone |
| Quantity |
10 µg |
| Quantitation Method |
Please see our FAQ |
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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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Sample Source
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DNA from Fibroblast
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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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| Passage Frozen |
6 |
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| alkaline phosphatase |
Weiss et al (Am J Hum Genet 44:686-694 1989) reported that this fibroblast culture from an individual affected with Hypophosphatasia had deficient liver/bone/kidney alkaline phosphatase activity but expressed apparently full-sized liver/bone/kidney mRNA at normal levels. Southern blot analysis of the liver/bone/kidney alkaline phosphatase gene revealed identical restriction patterns for this individual and normal controls. EC Number: 3.1.3.1 |
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| alkaline phosphatase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.1.3.1 |
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| Gene |
ALPL |
| Chromosomal Location |
1p36.1-p34 |
| Allelic Variant 1 |
171760.0002; HYPOPHOSPHATASIA, INFANTILE |
| Identified Mutation |
ARG54CYS; In studies of fibroblasts from 4 unrelated patients with severe (perinatal or infantile) hypophosphatasia (241500), Henthorn et al. [Proc. Nat. Acad. Sci. 89: 9924-9928 (1992)] identified a different mutation in each of the 8 ALPL alleles, indicating that all were genetic compounds. They found 2 linked polymorphisms in 1 allele of each patient. One allele found in cell line GM04235 was a C-to-T transition at nucleotide 387 in exon 4 leading to substitution of cysteine for arginine at amino acid 54. |
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| Gene |
ALPL |
| Chromosomal Location |
1p36.1-p34 |
| Allelic Variant 2 |
171760.0003; HYPOPHOSPHATASIA, INFANTILE |
| Identified Mutation |
ASP277ALA; Henthorn et al. [Proc. Nat. Acad. Sci. 89: 9924-9928 (1992)] found in 1 allele of the ALPL gene in cell line GM04235 an A-to-C transversion at nucleotide 1057 of exon 9 resulting in substitution of alanine for asp277. |
| Remarks |
Low serum alkaline phosphatase; high urinary phosphoethanolamine; a sib died at age 5 mos from same disease; shows bowing of the long bones & abnormal metaphyses; deficient fibroblast alkaline phosphatase activity; donor subject is a compound heterozygote for two mutations in the ALPL gene: one allele carries a C-to-T transition at nucleotide 387 (387C>T) in exon 4 leading to substitution of cysteine for arginine at amino acid 54 [ARG54CYS (R54C)] and a second allele carries a A-to-C transversion at nucleotide 1057 (1057A>C) of exon 9 resulting in substitution of alanine for asp277 [ASP277ALA (D227A). |
| Fedde KN, Michell MP, Henthorn PS, Whyte MP, Aberrant properties of alkaline phosphatase in patient fibroblasts correlate with clinical expressivity in severe forms of hypophosphatasia. J Clin Endocrinol Metab81:2587-94 1996 |
| PubMed ID: 8675582 |
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| Henthorn PS, Raducha M, Fedde KN, Lafferty MA, Whyte MP, Different missense mutations at the tissue-nonspecific alkaline phosphatase gene
locus in autosomal recessively inherited forms of mild and severe
hypophosphatasia. Proc Natl Acad Sci U S A89(20):9924-8 1992 |
| PubMed ID: 1409720 |
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| Weiss MJ, Ray K, Fallon MD, Whyte MP, Fedde KN, Lafferty MA, Mulivor RA, Harris H, Analysis of liver/bone/kidney alkaline phosphatase mRNA, DNA, and enzymatic activity in cultured skin fibroblasts from 14 unrelated patients with severe hypophosphatasia. Am J Hum Genet44:686-94 1989 |
| PubMed ID: 2705456 |
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| Whyte MP, Vrabel LA, Schwartz TD, Alkaline phosphatase deficiency in cultured skin fibroblasts from patients with hypophosphatasia: comparison of the infantile, childhood, and adult forms. J Clin Endocrinol Metab57:831-7 1983 |
| PubMed ID: 6885967 |
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