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Intermediate alpha1-antitrypsin deficiency resulting from a null gene (M-phenotype)
Chest
|October 1, 1976
Summary
A null gene for alpha1-antitrypsin can be inherited with a normal phenotype, leading to reduced antitrypsin levels. Quantitative testing is crucial for identifying this deficiency, as phenotyping alone is insufficient.
Area of Science:
- Genetics
- Pulmonology
- Biochemistry
Background:
- Alpha1-antitrypsin deficiency (AATD) is a genetic disorder that can lead to lung disease.
- The PiM phenotype is considered normal, while other phenotypes are associated with varying levels of AATD.
- Identifying all genetic variants, including null genes, is crucial for accurate diagnosis and management.
Observation:
- A family study identified a null gene for alpha1-antitrypsin.
- The null gene was inherited with a normal (PiM) phenotypic pattern, presenting as intermediate antitrypsin deficiency.
- The proband, a smoker with PiM phenotype, showed physiologic evidence of pulmonary emphysema.
Findings:
- Individuals with the M-phenotype and the null gene had significantly lower serum trypsin inhibitory capacity compared to those with the MZ phenotype.
- Estrogenic medication in some family members did not mask the deficient trypsin inhibitory capacity, suggesting an unresponsive gene.
- The null gene contributes no detectable antitrypsin activity to serum levels.
Implications:
- Quantitative measurement of alpha1-antitrypsin activity or concentration is essential for screening programs.
- Phenotyping alone is inadequate for detecting the null gene for alpha1-antitrypsin.
- Accurate identification of AATD, including null variants, is vital for genetic counseling and clinical management.
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