Single strand conformation polymorphism analysis of androgen receptor gene mutations in patients with androgen insensitivity syndromes: Application for diagnosis, genetic counseling, and therapy
- Medizinische Universitaet zu Luebeck (Germany) Tufts-New England Medical Center, Boston, MA (United States)
- Massachusetts Eye and Ear Infirmary, Boston, MA (United States)
- Medizinische Universitaet zu Luebeck (Germany)
- Tufts-New England Medical Center, Boston, MA (United States)
- Massachusetts Eye and Ear Infirmary, Boston, MA (United States); Harvard Medical School, Boston, MA (United States) Harvard School of Public Health, Boston, MA (United States)
Recent studies indicate that mutations in the androgen receptor gene are associated with androgen insensitivity syndromes, a heterogeneous group of related disorders involving defective sexual differentiation in karyotypic males. In this report, the authors address the possibility of rapid mutational analysis of the androgen receptor gene for initial diagnosis, genetic counseling, and molecular subclassification of affected patients and their families. DNA from peripheral blood leukocytes of six patients from five families with various degrees of androgen insensitivity was studied. Exons 2 to 8 of the androgen receptor gene were analyzed using a combination of single strand conformation polymorphism analysis and direct DNA sequencing. Female family members were also studied to identify heterozygote carriers. Point mutations in the AR gene were identified in all six patients, and all mutations caused amino acid substitutions. One patient with incomplete androgen insensitivity was a mosaic for the mutation. Four of the five mothers, as well as a young sister of one patient, were carriers of the mutation present in the affected child. The data show that new mutations may occur in the androgen receptor gene leading to sporadic androgen insensitivity syndrome. Molecular genetic characterization of the variant allele can serve as a primary tool for diagnosis and subsequent therapy, and can provide a basis for distinguishing heterozygous carriers in familial androgen resistance. The identification of carriers is of substantial clinical importance for genetic counseling. 29 refs., 2 figs., 1 tab.
- OSTI ID:
- 5647223
- Journal Information:
- Journal of Clinical Endocrinology and Metabolism; (United States), Vol. 77:1; ISSN 0021-972X
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANDROGENS
METABOLIC DISEASES
RECEPTORS
GENE MUTATIONS
DNA SEQUENCING
LEUKOCYTES
ANDROSTANES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
DISEASES
HORMONES
MATERIALS
MEMBRANE PROTEINS
MUTATIONS
ORGANIC COMPOUNDS
PROTEINS
STEROID HORMONES
STEROIDS
STRUCTURAL CHEMICAL ANALYSIS
550400* - Genetics