Genome analyses and androgen quantification for an infant with 5α-reductase type 2 deficiency

Kazuhisa Akiba; Keiko Aso; Yukihiro Hasegawa; Maki Fukami

doi:10.1515/jpem-2020-0678

Article

Genome analyses and androgen quantification for an infant with 5α-reductase type 2 deficiency

Kazuhisa Akiba , Keiko Aso , Yukihiro Hasegawa and Maki Fukami

Published/Copyright: June 24, 2021

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 34 Issue 9

Abstract

Objectives

5α-reductase type 2 deficiency due to biallelic SRD5A2 variants is a common form of 46,XY disorders of sex development.

Case presentation

A Chinese neonate presented with ambiguous genitalia. He carried a homozygous likely_pathogenic SRD5A2 variant (c.650C>A, p.A217E). His apparently nonconsanguineous parents were heterozygotes for the variant. The variant has previously been identified in two Chinese patients. Our patient carried 14.2 Mb loss-of-heterogeneity regions distributed in the genome. The SRD5A2 variant in this family was invariably coupled with two polymorphisms in exon 1 and intron 1. In the patient, blood testosterone (T)/5α-dihydrotestosterone (5αDHT) ratios were elevated before and during mini puberty, and were higher when measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) than measured by conventional immune assays.

Conclusions

This study provides evidence for the founder effect of an SRD5A2 variant. Furthermore, our data indicate that there is a need to establish a new reference value for T/5αDHT ratios using LC-MS/MS.

Keywords: founder mutation; LC-MS/MS; T/5αDHT ratio

Corresponding authors: Maki Fukami, MD, PhD, Department of Molecular Endocrinology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo 157-8535, Japan, Phone: +81 3 34160181, E-mail: fukami-m@ncchd.go.jp; and Yukihiro Hasegawa, MD, PhD, Division of Endocrinology and Metabolism, Tokyo Metropolitan Children’s Medical Center, Tokyo 183-8561, Japan, Phone: +81 42 3005111, E-mail: yhaset@gmail.com

Funding source: Japan Society for the Promotion of Science

Award Identifier / Grant number: 17H06428

Funding source: Japan Agency for Medical Research and Development

Award Identifier / Grant number: 20ek0109464h0001

Funding source: National Center for Child Health and Development

Award Identifier / Grant number: 2019A-1

Funding source: Takeda Science Foundation

Research funding: This study was supported by the Grants-in-Aid from JSPS (17H06428), AMED (20ek0109464h0001), National Center for Child Health and Development (2019A-1) and Takeda Science Foundation.
Author contributions: Ka.A. and Y.H. conceived the study. Ka.A., Ke.A., and Y.H performed clinical analyses. Ka.A. and M.F. performed molecular analysis and wrote the manuscript. All authors critically reviewed and revised the manuscript and approved the final version.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Informed consent: Informed consent was obtained from all individuals included in this case report.
Ethical approval: This study was approved by the Institutional Review Board Committee at the National Center for Child Health and Development and performed after obtaining written informed consent from the patient’s parents.

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Received: 2020-11-26

Accepted: 2021-05-10

Published Online: 2021-06-24

Published in Print: 2021-09-27

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Articles in the same Issue

https://doi.org/10.1515/jpem-2020-0678

Keywords for this article

founder mutation; LC-MS/MS; T/5αDHT ratio