Cargando…

In Tandem Intragenic Duplication of Doublesex and Mab-3-Related Transcription Factor 1 (DMRT1) in an SRY-Negative Boy with a 46,XX Disorder of Sex Development

Disorders of sexual development (DSDs) encompass a group of congenital conditions associated with atypical development of internal and external genital structures. Among those with DSDs are 46,XX males, whose condition mainly arises due to the translocation of SRY onto an X chromosome or an autosome...

Descripción completa

Detalles Bibliográficos
Autores principales: Bertini, Veronica, Baldinotti, Fulvia, Parma, Pietro, Tyutyusheva, Nina, Sepich, Margherita, Bertolucci, Giulia, Rosano, Camillo, Caligo, Maria Adelaide, Peroni, Diego, Valetto, Angelo, Bertelloni, Silvano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671459/
https://www.ncbi.nlm.nih.gov/pubmed/38003010
http://dx.doi.org/10.3390/genes14112067
_version_ 1785140161861910528
author Bertini, Veronica
Baldinotti, Fulvia
Parma, Pietro
Tyutyusheva, Nina
Sepich, Margherita
Bertolucci, Giulia
Rosano, Camillo
Caligo, Maria Adelaide
Peroni, Diego
Valetto, Angelo
Bertelloni, Silvano
author_facet Bertini, Veronica
Baldinotti, Fulvia
Parma, Pietro
Tyutyusheva, Nina
Sepich, Margherita
Bertolucci, Giulia
Rosano, Camillo
Caligo, Maria Adelaide
Peroni, Diego
Valetto, Angelo
Bertelloni, Silvano
author_sort Bertini, Veronica
collection PubMed
description Disorders of sexual development (DSDs) encompass a group of congenital conditions associated with atypical development of internal and external genital structures. Among those with DSDs are 46,XX males, whose condition mainly arises due to the translocation of SRY onto an X chromosome or an autosome. In the few SRY-negative 46,XX males, overexpression of other pro-testis genes or failure of pro-ovarian/anti-testis genes may be involved, even if a non-negligible number of cases remain unexplained. A three-year-old boy with an SRY-negative 46,XX karyotype showed a normal male phenotype and normal prepubertal values for testicular hormones. A heterozygous de novo in tandem duplication of 50,221 bp, which encompassed exons 2 and 3 of the Doublesex and Mab-3-related transcription factor 1 (DMRT1) gene, was detected using MPLA, CGH-array analysis, and Sanger sequencing. Both breakpoints were in the intronic regions, and this duplication did not stop or shift the coding frame. Additional pathogenic or uncertain variants were not found in a known pro-testis/anti-ovary gene cascade using a custom NGS panel and whole genome sequencing. The duplication may have allowed DMRT1 to escape the transcriptional repression that normally occurs in 46,XX fetal gonads and thus permitted the testicular determination cascade to switch on. So far, no case of SRY-negative 46,XX DSD with alterations in DMRT1 has been described.
format Online
Article
Text
id pubmed-10671459
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-106714592023-11-12 In Tandem Intragenic Duplication of Doublesex and Mab-3-Related Transcription Factor 1 (DMRT1) in an SRY-Negative Boy with a 46,XX Disorder of Sex Development Bertini, Veronica Baldinotti, Fulvia Parma, Pietro Tyutyusheva, Nina Sepich, Margherita Bertolucci, Giulia Rosano, Camillo Caligo, Maria Adelaide Peroni, Diego Valetto, Angelo Bertelloni, Silvano Genes (Basel) Case Report Disorders of sexual development (DSDs) encompass a group of congenital conditions associated with atypical development of internal and external genital structures. Among those with DSDs are 46,XX males, whose condition mainly arises due to the translocation of SRY onto an X chromosome or an autosome. In the few SRY-negative 46,XX males, overexpression of other pro-testis genes or failure of pro-ovarian/anti-testis genes may be involved, even if a non-negligible number of cases remain unexplained. A three-year-old boy with an SRY-negative 46,XX karyotype showed a normal male phenotype and normal prepubertal values for testicular hormones. A heterozygous de novo in tandem duplication of 50,221 bp, which encompassed exons 2 and 3 of the Doublesex and Mab-3-related transcription factor 1 (DMRT1) gene, was detected using MPLA, CGH-array analysis, and Sanger sequencing. Both breakpoints were in the intronic regions, and this duplication did not stop or shift the coding frame. Additional pathogenic or uncertain variants were not found in a known pro-testis/anti-ovary gene cascade using a custom NGS panel and whole genome sequencing. The duplication may have allowed DMRT1 to escape the transcriptional repression that normally occurs in 46,XX fetal gonads and thus permitted the testicular determination cascade to switch on. So far, no case of SRY-negative 46,XX DSD with alterations in DMRT1 has been described. MDPI 2023-11-12 /pmc/articles/PMC10671459/ /pubmed/38003010 http://dx.doi.org/10.3390/genes14112067 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Bertini, Veronica
Baldinotti, Fulvia
Parma, Pietro
Tyutyusheva, Nina
Sepich, Margherita
Bertolucci, Giulia
Rosano, Camillo
Caligo, Maria Adelaide
Peroni, Diego
Valetto, Angelo
Bertelloni, Silvano
In Tandem Intragenic Duplication of Doublesex and Mab-3-Related Transcription Factor 1 (DMRT1) in an SRY-Negative Boy with a 46,XX Disorder of Sex Development
title In Tandem Intragenic Duplication of Doublesex and Mab-3-Related Transcription Factor 1 (DMRT1) in an SRY-Negative Boy with a 46,XX Disorder of Sex Development
title_full In Tandem Intragenic Duplication of Doublesex and Mab-3-Related Transcription Factor 1 (DMRT1) in an SRY-Negative Boy with a 46,XX Disorder of Sex Development
title_fullStr In Tandem Intragenic Duplication of Doublesex and Mab-3-Related Transcription Factor 1 (DMRT1) in an SRY-Negative Boy with a 46,XX Disorder of Sex Development
title_full_unstemmed In Tandem Intragenic Duplication of Doublesex and Mab-3-Related Transcription Factor 1 (DMRT1) in an SRY-Negative Boy with a 46,XX Disorder of Sex Development
title_short In Tandem Intragenic Duplication of Doublesex and Mab-3-Related Transcription Factor 1 (DMRT1) in an SRY-Negative Boy with a 46,XX Disorder of Sex Development
title_sort in tandem intragenic duplication of doublesex and mab-3-related transcription factor 1 (dmrt1) in an sry-negative boy with a 46,xx disorder of sex development
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10671459/
https://www.ncbi.nlm.nih.gov/pubmed/38003010
http://dx.doi.org/10.3390/genes14112067
work_keys_str_mv AT bertiniveronica intandemintragenicduplicationofdoublesexandmab3relatedtranscriptionfactor1dmrt1inansrynegativeboywitha46xxdisorderofsexdevelopment
AT baldinottifulvia intandemintragenicduplicationofdoublesexandmab3relatedtranscriptionfactor1dmrt1inansrynegativeboywitha46xxdisorderofsexdevelopment
AT parmapietro intandemintragenicduplicationofdoublesexandmab3relatedtranscriptionfactor1dmrt1inansrynegativeboywitha46xxdisorderofsexdevelopment
AT tyutyushevanina intandemintragenicduplicationofdoublesexandmab3relatedtranscriptionfactor1dmrt1inansrynegativeboywitha46xxdisorderofsexdevelopment
AT sepichmargherita intandemintragenicduplicationofdoublesexandmab3relatedtranscriptionfactor1dmrt1inansrynegativeboywitha46xxdisorderofsexdevelopment
AT bertoluccigiulia intandemintragenicduplicationofdoublesexandmab3relatedtranscriptionfactor1dmrt1inansrynegativeboywitha46xxdisorderofsexdevelopment
AT rosanocamillo intandemintragenicduplicationofdoublesexandmab3relatedtranscriptionfactor1dmrt1inansrynegativeboywitha46xxdisorderofsexdevelopment
AT caligomariaadelaide intandemintragenicduplicationofdoublesexandmab3relatedtranscriptionfactor1dmrt1inansrynegativeboywitha46xxdisorderofsexdevelopment
AT peronidiego intandemintragenicduplicationofdoublesexandmab3relatedtranscriptionfactor1dmrt1inansrynegativeboywitha46xxdisorderofsexdevelopment
AT valettoangelo intandemintragenicduplicationofdoublesexandmab3relatedtranscriptionfactor1dmrt1inansrynegativeboywitha46xxdisorderofsexdevelopment
AT bertellonisilvano intandemintragenicduplicationofdoublesexandmab3relatedtranscriptionfactor1dmrt1inansrynegativeboywitha46xxdisorderofsexdevelopment