Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Intragenic Duplication of DMRT1 in a SRY-Negative Boy with 46,XX Disorder of Sex Development

Version 1 : Received: 9 December 2021 / Approved: 14 December 2021 / Online: 14 December 2021 (07:58:55 CET)

How to cite: Bertini, V.; Baldinotti, F.; Tyutyusheva, N.; Rosano, C.; Cosini, C.; Caligo, A.M.; Peroni, D.; Valetto, A.; Bertelloni, S. Intragenic Duplication of DMRT1 in a SRY-Negative Boy with 46,XX Disorder of Sex Development. Preprints 2021, 2021120219 (doi: 10.20944/preprints202112.0219.v1). Bertini, V.; Baldinotti, F.; Tyutyusheva, N.; Rosano, C.; Cosini, C.; Caligo, A.M.; Peroni, D.; Valetto, A.; Bertelloni, S. Intragenic Duplication of DMRT1 in a SRY-Negative Boy with 46,XX Disorder of Sex Development. Preprints 2021, 2021120219 (doi: 10.20944/preprints202112.0219.v1).

Abstract

Background. 46,XX disorders of sex development are rare. Approximately, 90% of XX males are SRY-positive, while testicular development in the absence of SRY takes place in a minority. Methods: A boy with 46,XX karyotype (SRY-negative; absence of SOX9 duplications) was investigated by targeted Next Generation Sequencing (NGS), Multiplex ligation-dependent probe amplification (MLPA), and Comparative Genomic Hybridization array (CGH-array). Results: The boy had normal male phenotype and normal prepubertal values of testicular hormones. He presented a heterozygous duplication of 49.626 bp, encompassing exons 2 and 3 of DMRT1. The result was arr[GRCh37] 9p24.3(845893_895518)x3. Since both breakpoints are harbored in the intronic regions, the duplication does not stop or shift the coding frame. Additional known pathogenic or uncertain variants in pro-testis gene cascade were not identified. Conclusions: This study report a boy with 46,XX testicular disorder of sex differentiation, showing a de novo partial intragenic duplication of DMRT1. This intragenic duplication may result in a gain of function, acting as primary pro-testis gene (or anti-ovary gene) in a 46,XX human foetus and permitting normal pre-pubertal endocrine testis function.

Keywords

46,XX disorder of sex development; SRY-negative male; Testis determination; DMRT1; DMRT1 duplication

Subject

MEDICINE & PHARMACOLOGY, Pediatrics

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