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A mutation c.C2812T in the androgen receptor gene resulting in Pro817Leu substitution may affect dimerization of the androgen receptor and result in androgen insensitivity syndrome.
Fertil Steril. 2006 Jun; 85(6):1822.e1-4.FS

Abstract

OBJECTIVE

To conduct clinical, genetic, and molecular diagnostics of two sisters with typical symptoms of complete androgen insensitivity syndrome.

DESIGN

Case report.

SETTING

Research laboratory at a university of medical science.

PATIENT(S)

Two patients with 46,XY karyotype and a female phenotype were diagnosed because of primary amenorrhea. Their sister with 46,XX karyotype, her daughter, and five other family members including their mother also were examined.

INTERVENTION(S)

Orchiectomy, estrogen substitution therapy.

MAIN OUTCOME MEASURE(S)

Cancer prophylaxis.

RESULT(S)

Multiple-temperature single-stranded conformation polymorphism and sequence analyses of the androgen receptor gene (AR) revealed a c.C2812T transition in exon 7 in the two sisters. Their mother and the third sister (46,XX) were carriers of the same mutation. This mutation, which previously had never been reported, resulted in Pro817Leu substitution in the ligand-binding domain of the androgen. Computer simulation of structural changes generated by Pro817Leu substitution revealed appreciable conformational changes in the region responsible for dimerization of the receptor.

CONCLUSION(S)

The novel c.C2812T transition that might impair dimerization of the receptor is responsible for the clinical symptoms of complete androgen insensitivity syndrome in the affected individuals. Molecular analysis of AR proved to be very useful for genetic counseling of the unaffected sister, who was a carrier of the same mutation.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, University of Medical Sciences, Poznan, Poland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16759930

Citation

Turek-Plewa, Justyna, et al. "A Mutation c.C2812T in the Androgen Receptor Gene Resulting in Pro817Leu Substitution May Affect Dimerization of the Androgen Receptor and Result in Androgen Insensitivity Syndrome." Fertility and Sterility, vol. 85, no. 6, 2006, pp. 1822.e1-4.
Turek-Plewa J, Eckersdorf-Mastalerz A, Kaluzewski B, et al. A mutation c.C2812T in the androgen receptor gene resulting in Pro817Leu substitution may affect dimerization of the androgen receptor and result in androgen insensitivity syndrome. Fertil Steril. 2006;85(6):1822.e1-4.
Turek-Plewa, J., Eckersdorf-Mastalerz, A., Kaluzewski, B., Helszer, Z., & Trzeciak, W. H. (2006). A mutation c.C2812T in the androgen receptor gene resulting in Pro817Leu substitution may affect dimerization of the androgen receptor and result in androgen insensitivity syndrome. Fertility and Sterility, 85(6), e1-4.
Turek-Plewa J, et al. A Mutation c.C2812T in the Androgen Receptor Gene Resulting in Pro817Leu Substitution May Affect Dimerization of the Androgen Receptor and Result in Androgen Insensitivity Syndrome. Fertil Steril. 2006;85(6):1822.e1-4. PubMed PMID: 16759930.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A mutation c.C2812T in the androgen receptor gene resulting in Pro817Leu substitution may affect dimerization of the androgen receptor and result in androgen insensitivity syndrome. AU - Turek-Plewa,Justyna, AU - Eckersdorf-Mastalerz,Anna, AU - Kaluzewski,Bogdan, AU - Helszer,Zofia, AU - Trzeciak,Wieslaw H, PY - 2005/07/21/received PY - 2005/11/29/revised PY - 2005/11/29/accepted PY - 2006/6/9/pubmed PY - 2006/6/28/medline PY - 2006/6/9/entrez SP - 1822.e1 EP - 4 JF - Fertility and sterility JO - Fertil Steril VL - 85 IS - 6 N2 - OBJECTIVE: To conduct clinical, genetic, and molecular diagnostics of two sisters with typical symptoms of complete androgen insensitivity syndrome. DESIGN: Case report. SETTING: Research laboratory at a university of medical science. PATIENT(S): Two patients with 46,XY karyotype and a female phenotype were diagnosed because of primary amenorrhea. Their sister with 46,XX karyotype, her daughter, and five other family members including their mother also were examined. INTERVENTION(S): Orchiectomy, estrogen substitution therapy. MAIN OUTCOME MEASURE(S): Cancer prophylaxis. RESULT(S): Multiple-temperature single-stranded conformation polymorphism and sequence analyses of the androgen receptor gene (AR) revealed a c.C2812T transition in exon 7 in the two sisters. Their mother and the third sister (46,XX) were carriers of the same mutation. This mutation, which previously had never been reported, resulted in Pro817Leu substitution in the ligand-binding domain of the androgen. Computer simulation of structural changes generated by Pro817Leu substitution revealed appreciable conformational changes in the region responsible for dimerization of the receptor. CONCLUSION(S): The novel c.C2812T transition that might impair dimerization of the receptor is responsible for the clinical symptoms of complete androgen insensitivity syndrome in the affected individuals. Molecular analysis of AR proved to be very useful for genetic counseling of the unaffected sister, who was a carrier of the same mutation. SN - 1556-5653 UR - https://www.unboundmedicine.com/medline/citation/16759930/A_mutation_c_C2812T_in_the_androgen_receptor_gene_resulting_in_Pro817Leu_substitution_may_affect_dimerization_of_the_androgen_receptor_and_result_in_androgen_insensitivity_syndrome_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0015-0282(06)00495-X DB - PRIME DP - Unbound Medicine ER -