GM04235

GM04235 Fibroblast

Description:

HYPOPHOSPHATASIA, INFANTILE
ALKALINE PHOSPHATASE, LIVER; ALPL

Affected:

Yes

Sex:

Male

Age:

5 MO (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Connective Tissue, Muscle, and Bone

Cell Type

Fibroblast

Transformant

Untransformed

Race

White

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

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).

Characterizations

Passage Frozen

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

alkaline phosphatase

According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 3.1.3.1

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.

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.

Phenotypic Data

Remarks

Publications

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

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

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

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