A Novel Look at Dosage-Sensitive Sex Locus Xp21.2 in a Case of 46,XY Partial Gonadal Dysgenesis without NR0B1 Duplication

Ana Paula Francese-Santos; Jakob A Meinel; Cristiane S C Piveta; Juliana G R Andrade; Beatriz A Barros; Helena Fabbri-Scallet; Vera Lúcia Gil-da-Silva-Lopes; Gil Guerra-Junior; Axel Künstner; Hauke Busch; Olaf Hiort; Maricilda P de Mello; Ralf Werner; Andréa T Maciel-Guerra

doi:10.3390/ijms24010494

A Novel Look at Dosage-Sensitive Sex Locus Xp21.2 in a Case of 46,XY Partial Gonadal Dysgenesis without NR0B1 Duplication

Int J Mol Sci. 2022 Dec 28;24(1):494. doi: 10.3390/ijms24010494.

Authors

Ana Paula Francese-Santos^{1

2}, Jakob A Meinel³, Cristiane S C Piveta², Juliana G R Andrade^{4

5}, Beatriz A Barros^{4

5}, Helena Fabbri-Scallet^{2

4}, Vera Lúcia Gil-da-Silva-Lopes¹, Gil Guerra-Junior^{4

5}, Axel Künstner⁶, Hauke Busch⁶, Olaf Hiort³, Maricilda P de Mello^{2

4}, Ralf Werner^{3

7}, Andréa T Maciel-Guerra^{1

4}

Affiliations

¹ Department of Translational Medicine, State University of Campinas (UNICAMP), Campinas 13083-888, SP, Brazil.
² Molecular Biology and Genetic Engineering Center, State University of Campinas (UNICAMP), Campinas 13083-875, SP, Brazil.
³ Department of Pediatrics and Adolescent Medicine, Division of Paediatric Endocrinology and Diabetes, University of Lübeck, 23562 Lübeck, Germany.
⁴ Interdisciplinary Group for the Study of Sex Determination and Differentiation (GIEDDS), State University of Campinas (UNICAMP), Campinas 13083-888, SP, Brazil.
⁵ Department of Pediatrics, State University of Campinas (UNICAMP), Campinas 13083-888, SP, Brazil.
⁶ Group of Medical Systems Biology, Lübeck Institute of Experimental Dermatology, University of Lübeck, 23562 Lübeck, Germany.
⁷ Institute of Molecular Medicine, University of Lübeck, 23562 Lübeck, Germany.

Abstract

A region of 160 kb at Xp21.2 has been defined as dosage-sensitive sex reversal (DSS) and includes the NR0B1 gene, considered to be the candidate gene involved in XY gonadal dysgenesis if overexpressed. We describe a girl with 46,XY partial gonadal dysgenesis carrying a 297 kb duplication at Xp21.2 upstream of NR0B1 initially detected by chromosomal microarray analysis. Fine mapping of the breakpoints by whole-genome sequencing showed a tandem duplication of TASL (CXorf21), GK and partially TAB3, upstream of NR0B1. This is the first description of an Xp21.2 duplication upstream of NR0B1 associated with 46,XY partial gonadal dysgenesis.

Keywords: 46,XY partial gonadal dysgenesis; NR0B1; Xp21.2 duplication; chromosome microarray analysis; disorders of sex development; whole-genome sequencing.

Publication types

Case Reports

MeSH terms

DAX-1 Orphan Nuclear Receptor / genetics
Female
Gonadal Dysgenesis, 46,XY* / genetics
Humans

Substances

DAX-1 Orphan Nuclear Receptor
NR0B1 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding