Predicting puberty in partial androgen insensitivity syndrome: Use of clinical and functional androgen receptor indices.
Hughes, Ieuan A
MetadataShow full item record
Lek, N., Tadokoro-Cuccaro, R., Whitchurch, J. B., Mazumder, B., Miles, H., Prentice, P., Bunch, T., et al. (2018). Predicting puberty in partial androgen insensitivity syndrome: Use of clinical and functional androgen receptor indices.. EBioMedicine, 36 401-409. https://doi.org/10.1016/j.ebiom.2018.09.047
BACKGROUND: PAIS exhibits a complex spectrum of phenotypes and pubertal outcomes. The paucity of reliable prognostic indicators can confound management decisions including sex-of-rearing. We assessed whether external masculinisation score (EMS) at birth or functional assays correlates with pubertal outcome in PAIS patients and whether the EMS is helpful in sex assignment. METHODS: We collected pubertal outcome data for 27 male-assigned PAIS patients, all with confirmed androgen receptor (AR) mutations, including two previously uncharacterized variants (I899F; Y916C). Patients were grouped as follows; EMS at birth <5 and ≥ 5 (EMS in normal males is 12; median EMS in PAIS is 4·7) and pubertal outcomes compared. FINDINGS: Only 6/9 patients (67%) with EMS <5 underwent spontaneous onset of puberty, versus all 18 patients with EMS ≥5 (p = .03). Only 1/6 patients (17%) with EMS <5 developed adult genitalia reaching Tanner stage 4 or 5, versus 11/13 (85%) with EMS ≥5 (p = 0·01). There was no significant difference between the two groups of patients in being prescribed androgen replacement, who reached adult testicular volume ≥ 15 ml, pubic hair Tanner stage 4 or 5, above average adult height, had gynaecomastia, and mastectomy. No correlation was observed between EMS and in vitro AR function. INTERPRETATION: In PAIS with AR mutation, birth EMS is a simple predictor of spontaneous pubertal onset and satisfactory adult genitalia. This provides useful information when discussing the likely options for management at puberty. FUND: European Commission Framework 7 Programme, NIHR Cambridge Biomedical Research Centre, BBSRC DTP.
Androgen insensitivity, Androgen receptor, External masculinisation score, Gynaecomastia, Mutation, Puberty outcome, Reporter assays, Sex assignment, in silico modelling, Adolescent, Adult, Alleles, Androgen-Insensitivity Syndrome, Animals, Biomarkers, Cell Line, Gene Expression, Genotype, Humans, Male, Mutation, Puberty, Receptors, Androgen, Young Adult
External DOI: https://doi.org/10.1016/j.ebiom.2018.09.047
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285520
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: email@example.com