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A new missense substitution at a mutational hot spot of the androgen receptor in siblings with complete androgen insensitivity syndrome.
Hum Mutat. 1998; 11(4):337-9.HM

Abstract

Several mutations have been described in the human androgen receptor gene including constitutional mutations in androgen insensitivity syndrome, somatic mutations in prostate cancer and triplet expansions in Kennedy's disease (Gottlieb et al. 1997). Here we report on two siblings with complete androgen insensitivity and a novel missense mutation, D695V, in their androgen receptor gene. The two XY females are siblings of German descent and presented at the ages of 23 and 19 years, respectively, with typical clinical features of complete androgen insensitivity. We found both siblings to be hemizygous for a new adenine to thymine transversion at the second nucleotide of codon 695 within the fourth exon of the human androgen receptor gene. The resulting missense mutation D695V is located at the amino-terminal border of the ligand-binding domain of the androgen receptor. The aspartic acid residue at this position is highly conserved in the steroid binding domains of other members of the nuclear receptor family and has already been found to be the site of two other missense mutations associated with androgen insensitivity syndrome (Ris Stalpers et al. 1991, Hiort et al. 1996). Three of four reported subjects showed the complete androgen insensitivity phenotype, in accordance with the two siblings in our study. We suggest that the existence of three pathological amino acid substitutions for aspartic acid 695 most likely reflects the essential role of this residue for normal androgen receptor function in male sexual differentiation.

Authors+Show Affiliations

Institute of Human Genetics, Medical School Hanover, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

9554754

Citation

Dörk, T, et al. "A New Missense Substitution at a Mutational Hot Spot of the Androgen Receptor in Siblings With Complete Androgen Insensitivity Syndrome." Human Mutation, vol. 11, no. 4, 1998, pp. 337-9.
Dörk T, Schnieders F, Jakubiczka S, et al. A new missense substitution at a mutational hot spot of the androgen receptor in siblings with complete androgen insensitivity syndrome. Hum Mutat. 1998;11(4):337-9.
Dörk, T., Schnieders, F., Jakubiczka, S., Wieacker, P., Schroeder-Kurth, T., & Schmidtke, J. (1998). A new missense substitution at a mutational hot spot of the androgen receptor in siblings with complete androgen insensitivity syndrome. Human Mutation, 11(4), 337-9.
Dörk T, et al. A New Missense Substitution at a Mutational Hot Spot of the Androgen Receptor in Siblings With Complete Androgen Insensitivity Syndrome. Hum Mutat. 1998;11(4):337-9. PubMed PMID: 9554754.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A new missense substitution at a mutational hot spot of the androgen receptor in siblings with complete androgen insensitivity syndrome. AU - Dörk,T, AU - Schnieders,F, AU - Jakubiczka,S, AU - Wieacker,P, AU - Schroeder-Kurth,T, AU - Schmidtke,J, PY - 1998/4/29/pubmed PY - 1998/4/29/medline PY - 1998/4/29/entrez SP - 337 EP - 9 JF - Human mutation JO - Hum Mutat VL - 11 IS - 4 N2 - Several mutations have been described in the human androgen receptor gene including constitutional mutations in androgen insensitivity syndrome, somatic mutations in prostate cancer and triplet expansions in Kennedy's disease (Gottlieb et al. 1997). Here we report on two siblings with complete androgen insensitivity and a novel missense mutation, D695V, in their androgen receptor gene. The two XY females are siblings of German descent and presented at the ages of 23 and 19 years, respectively, with typical clinical features of complete androgen insensitivity. We found both siblings to be hemizygous for a new adenine to thymine transversion at the second nucleotide of codon 695 within the fourth exon of the human androgen receptor gene. The resulting missense mutation D695V is located at the amino-terminal border of the ligand-binding domain of the androgen receptor. The aspartic acid residue at this position is highly conserved in the steroid binding domains of other members of the nuclear receptor family and has already been found to be the site of two other missense mutations associated with androgen insensitivity syndrome (Ris Stalpers et al. 1991, Hiort et al. 1996). Three of four reported subjects showed the complete androgen insensitivity phenotype, in accordance with the two siblings in our study. We suggest that the existence of three pathological amino acid substitutions for aspartic acid 695 most likely reflects the essential role of this residue for normal androgen receptor function in male sexual differentiation. SN - 1059-7794 UR - https://www.unboundmedicine.com/medline/citation/9554754/A_new_missense_substitution_at_a_mutational_hot_spot_of_the_androgen_receptor_in_siblings_with_complete_androgen_insensitivity_syndrome_ L2 - http://www.diseaseinfosearch.org/result/436 DB - PRIME DP - Unbound Medicine ER -