An investigation of androgen-responsive non-coding RNAs in boys with atypical genitalia without genetic variants in the androgen receptor (AR)

Malika Alimussina; Martin McMillan; Sandra Chudleigh; Jane D McNeilly; Louise A Diver; Ruth McGowan; Edward S Tobias; Ahmed S Faisal

doi:10.1530/endoabs.77.P111

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Endocrine Abstracts (2021) 77 P111 | DOI: 10.1530/endoabs.77.P111

SFEBES2021 Poster Presentations Reproductive Endocrinology (31 abstracts)

An investigation of androgen-responsive non-coding RNAs in boys with atypical genitalia without genetic variants in the androgen receptor (AR)

Malika Alimussina ¹ , Martin McMillan ¹ , Sandra Chudleigh ² , Jane D McNeilly ³ , Louise A Diver ² , Ruth McGowan ^1,2 , Edward S Tobias ^2,4 & S Faisal Ahmed ¹

Err

Author affiliations

¹Developmental Endocrinology Research Group, University of Glasgow, Royal Hospital for Children, Glasgow, United Kingdom; ²West of Scotland Centre for Genomic Medicine, Queen Elizabeth University Hospital, Glasgow, United Kingdom; ³Biochemistry Department, Queen Elizabeth University Hospital, Glasgow, United Kingdom; ⁴Academic Medical Genetics and Clinical Pathology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, United Kingdom

Introduction: Transcriptome analysis of peripheral blood mononuclear cells (PBMC) RNA has identified a set of androgen-responsive non-coding RNAs.

Aim: To quantify the androgen-responsive gene expression and investigate its relationship to the testosterone (T) rise following hCG stimulation in boys with no genetic evidence of androgen insensitivity.

Methods: Boys with suspected DSD who were evaluated at the Royal Hospital for Children, Glasgow from 2018 to 2021 were included. Information on clinical, biochemical and genetic assessment was obtained from clinical records. PBMC RNA was collected before and after hCG stimulation of the testes on day 4(D4) and day 22(D22) and gene expression was quantified using QuantStudio^TM 3D Digital PCR.

Results: Ten XY boys with atypical genitalia, a median age of 0.8yrs(0.5,3.4) and no detected AR variants were included. The median baseline and peak T was 0.5nmol/l(0.5,6.8) and 21.7nmol/l(1.2,42.1), respectively. Within this group, there was one patient who did not show a T response to hCG at all on D4 and a minimal response on D22(1.2nmol/l). The median fold change in SNORD5and RNY5 on D4 in this patient was 0.09 and 0.05, respectively. The median fold change for the two genes on D22 was 0.14 and 0.04, respectively. In the rest of the cohort, the median post-hCG T on D4andD22 was 16 nmol/l(2.5,42) and 25 nmol/l(17,37), respectively. In this group, the median fold change in SNORD5expression on D4andD22 was 4.0(0.25,14) and 1.2(0.1,5.6), respectively. The median fold change in RNY5expression on D4andD22 was 1.0(0.1,38) and 0.5(0.2,7.7), respectively.

Conclusions: Expression levels of RNY5 and SNORD5 can be quantified accurately and show androgen dependency. Further research in genetically confirmed cases of androgen insensitivity plus those with no response to hCG stimulation is required to determine the diagnostic role of non-coding RNAs in XYDSD.