58 MOLECULAR BASIS OF INHERITED MYOADENYIATE DEAMINASE (AMP-D) DEFICIENCY
| Autor: | P. R. H. Clarke, Richard L. Sabina, Edward W. Holmes, William N Fishbein |
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| Rok vydání: | 1988 |
| Předmět: | |
| Zdroj: | Pediatric Research. 24:120-120 |
| ISSN: | 1530-0447 0031-3998 |
| Popis: | Inherited AMP-D deficiency is associated with a myopathy characterized by easy fatigability and myalgias. Deficiency of AMP-D is restricted to skeletal muscle and is associated with a decrease in the abundance of immunoreactive muscle-specific peptide. To define the molecular basis for this abnormality we have cloned cDNAs for the skeletal muscle-specific isoforms of human and rat AMP-D. We have made the following observations regarding AMP-D expression in a rodent model and in AMP-D deficient patients: 1) A single gene encodes AMP-D. 2) Two AMP-D transcripts are noted during muscle development in vivo and during myocyte differentiation in vitro. Rat fetal muscle contains an “embryonic” transcript (3.4 Kb) and peptide; postnatal skeletal muscle contains an “adult” transcript (2.5 Kb) and peptide. The latter are restricted to striated muscle. Production of the adult peptide is controlled by transcript switching, increase in transcript abundance during muscle development and possibly efficiency of translation. 3) Four patients with inherited deficiency of AMP-D have been evaluated with these probes. Although immunoreactive peptide is absent from their skeletal muscle, the abundance of the 2.5 Kb muscle-specific transcript is normal. We conclude from these studies that 1). AMP-D expression is controlled at multiple steps during myocyte development 2) Inherited deficiency of the muscle-specific isoform cannot be explained by a defect in transcript switching or rate of transcription, suggesting a defect in translation or a single base substitution. |
| Databáze: | OpenAIRE |
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