Biochemical and Biophysical Research Communications
Dissecting phenotypic variation among AIS patients☆
Section snippets
Materials and methods
Family and patients. A large Chinese family, which consisted of a total of 132 members across five generations, 14 males of them affected with AIS, was described in our previous genetic analysis. It showed that the patients in the pedigree shared an identical Arg840Cys substitution in the androgen receptor but displayed divergent disease phenotypes [12]. The patients who donated their genital skin tissues for the present study included the proband IV54 (cell strain MJ), who was fertile but was
Expression of AR in GSF cell lines
Fig. 1 shows Northern (A) and Western (B) blotting assays of AR in the GSF cell lines from the three AIS patients in the same family and from one independent normal donor. It does not reveal any viewable change in both transcriptional and translational levels of the AR gene among the four cell lines (N, MJ, YS, and ZGJ). The data first exclude the possibility of ascribing the divergent disease phenotypes of the three patients to any variation in the mRNA and protein levels of the mutant that
Discussion
There have been more than 300 mutations in the human androgen receptor gene [22]. Understanding the genetic effects of these mutants on the development of human maleness has been one of the active areas in human molecular genetics and reproductive physiology [20], [23], [24]. Many studies have focused on correlating the different mutants to different disease phenotypes of androgen insensitivity syndrome, based either on a few sporadic cases and/or on exogenous, such as COS or CV1, cells.
Acknowledgment
We are grateful to the patients for their participation and cooperation in the present study.
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Androgen insensitivity syndrome
2012, The LancetCitation Excerpt :Typically, binding is absent in complete androgen insensitivity syndrome and binding affinity (Kd) is altered in partial and mild androgen insensitivity syndrome. Genital skin fibroblasts can be used to identify genomic mutations that disrupt normal RNA splicing, quantify androgen receptor expression by western blots, and study the phenotypic variance recorded between patients with the same mutation.44,45 Automated DNA sequencing of the coding region and splice sites of the androgen receptor gene is now routinely available in the UK.
Clinical outcomes and genotype-phenotype correla-tions in patients with complete and partial androgen insensitivity syndromes
2023, Annals of Pediatric Endocrinology and MetabolismPathophysiological implications of androgen receptor. Mutations, polymorphisms and pathologic associations
2015, Revista Argentina de Endocrinologia y MetabolismoCell-line and tissue-specific signatures of androgen receptor-coregulator transcription
2006, Journal of Molecular MedicineIsolation and characterization of a novel four-transmembrane protein PMP22CD specifically expressed in the testis
2006, International Journal of Molecular Sciences
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The research was supported in part by grants from China’s Key Basic Research Program (“973”) and China’s National Natural Science Foundation. Z.W.L. is also supported by research grants from the Medical Research Committee of the University of Birmingham, BBSRC, and NERC.