Digenic Origin of Difference of Sex Development in a Patient Harbouring DHX37 and MAMLD1 Variants

Background. The diagnostic process for identifying variations in sex development (DSD) remains challenging due to the limited availability of evidence pertaining to the association between phenotype and genotype. DSD incidence is reported as 2 in 10,000 births, and the etiology has been attributed t...

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Main Authors: Katia Margiotti, Francesco Libotte, Marco Fabiani, Alvaro Mesoraca, Claudio Giorlandino
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:Case Reports in Pediatrics
Online Access:http://dx.doi.org/10.1155/2024/4896940
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author Katia Margiotti
Francesco Libotte
Marco Fabiani
Alvaro Mesoraca
Claudio Giorlandino
author_facet Katia Margiotti
Francesco Libotte
Marco Fabiani
Alvaro Mesoraca
Claudio Giorlandino
author_sort Katia Margiotti
collection DOAJ
description Background. The diagnostic process for identifying variations in sex development (DSD) remains challenging due to the limited availability of evidence pertaining to the association between phenotype and genotype. DSD incidence is reported as 2 in 10,000 births, and the etiology has been attributed to genetic causes. Case Presentation. The present study investigated genetic causes implicated in a case of a 15-year-old 46, XY patient, raised as a girl. Genetic analysis by clinical exome sequencing (CES) showed a digenic inheritance due to two known pathogenic mutations in the DHX37 gene and the MAMLD1 gene, while we excluded variants with pathogenic significance in 209 DSD-related genes. Conclusions. Based on our literature review, this is the first case with the combined presence of pathogenic mutations in the MAMLD1 gene and DHX37 gene in a patient with gonadal dysgenesis.
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series Case Reports in Pediatrics
spelling doaj-art-82c6d548fe77466e9f34fc1d60e075aa2025-08-20T03:37:57ZengWileyCase Reports in Pediatrics2090-68112024-01-01202410.1155/2024/4896940Digenic Origin of Difference of Sex Development in a Patient Harbouring DHX37 and MAMLD1 VariantsKatia Margiotti0Francesco Libotte1Marco Fabiani2Alvaro Mesoraca3Claudio Giorlandino4ALTAMEDICAALTAMEDICAALTAMEDICAALTAMEDICAALTAMEDICABackground. The diagnostic process for identifying variations in sex development (DSD) remains challenging due to the limited availability of evidence pertaining to the association between phenotype and genotype. DSD incidence is reported as 2 in 10,000 births, and the etiology has been attributed to genetic causes. Case Presentation. The present study investigated genetic causes implicated in a case of a 15-year-old 46, XY patient, raised as a girl. Genetic analysis by clinical exome sequencing (CES) showed a digenic inheritance due to two known pathogenic mutations in the DHX37 gene and the MAMLD1 gene, while we excluded variants with pathogenic significance in 209 DSD-related genes. Conclusions. Based on our literature review, this is the first case with the combined presence of pathogenic mutations in the MAMLD1 gene and DHX37 gene in a patient with gonadal dysgenesis.http://dx.doi.org/10.1155/2024/4896940
spellingShingle Katia Margiotti
Francesco Libotte
Marco Fabiani
Alvaro Mesoraca
Claudio Giorlandino
Digenic Origin of Difference of Sex Development in a Patient Harbouring DHX37 and MAMLD1 Variants
Case Reports in Pediatrics
title Digenic Origin of Difference of Sex Development in a Patient Harbouring DHX37 and MAMLD1 Variants
title_full Digenic Origin of Difference of Sex Development in a Patient Harbouring DHX37 and MAMLD1 Variants
title_fullStr Digenic Origin of Difference of Sex Development in a Patient Harbouring DHX37 and MAMLD1 Variants
title_full_unstemmed Digenic Origin of Difference of Sex Development in a Patient Harbouring DHX37 and MAMLD1 Variants
title_short Digenic Origin of Difference of Sex Development in a Patient Harbouring DHX37 and MAMLD1 Variants
title_sort digenic origin of difference of sex development in a patient harbouring dhx37 and mamld1 variants
url http://dx.doi.org/10.1155/2024/4896940
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