Case Report: De novo DHX37 mutations in Saudi patients with 46,XY differences of sex development
Differences of sex development (DSD) are a group of congenital conditions involving atypical chromosomal, gonadal, or anatomical sex development. DHX37, a gene involved in ribosome biogenesis, located on chromosome 12, at the 12q24.31 region, has recently emerged as a contributor to 46,XY DSD, parti...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1622036/full |
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| author | Abeer Alabduljabbar Sara Abid Dania Farooq Sara Aljazaeri Yara Khamag Raghad Alhuthil Latifah Alfahad Afaf Alsagheir Afaf Alsagheir |
| author_facet | Abeer Alabduljabbar Sara Abid Dania Farooq Sara Aljazaeri Yara Khamag Raghad Alhuthil Latifah Alfahad Afaf Alsagheir Afaf Alsagheir |
| author_sort | Abeer Alabduljabbar |
| collection | DOAJ |
| description | Differences of sex development (DSD) are a group of congenital conditions involving atypical chromosomal, gonadal, or anatomical sex development. DHX37, a gene involved in ribosome biogenesis, located on chromosome 12, at the 12q24.31 region, has recently emerged as a contributor to 46,XY DSD, particularly gonadal dysgenesis and testicular regression syndrome (TRS). This study presents a case series from Saudi Arabia highlighting novel and known DHX37 variants in three patients with 46,XY DSD. Three Saudi patients presented with ambiguous genitalia, non-palpable or atrophic testes, and hypergonadotropic hypogonadism. Identified variants included two known (p.Arg308Gln, p.Arg674Trp) and one novel (p.Gly478Val) missense mutation. Phenotypic variability ranged from complete testicular regression to partial gonadal dysgenesis. Thus, this is the first case series of DHX37-related DSD in Saudi Arabia, expanding the mutational spectrum and reinforcing the gene’s role in testicular development. Genetic testing, particularly whole-exome sequencing, is essential for accurate diagnosis and management, especially in regions with high consanguinity. |
| format | Article |
| id | doaj-art-70f186f6791a4b9389eb8d28fa7e8ff3 |
| institution | DOAJ |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj-art-70f186f6791a4b9389eb8d28fa7e8ff32025-08-20T02:41:23ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-07-011610.3389/fendo.2025.16220361622036Case Report: De novo DHX37 mutations in Saudi patients with 46,XY differences of sex developmentAbeer Alabduljabbar0Sara Abid1Dania Farooq2Sara Aljazaeri3Yara Khamag4Raghad Alhuthil5Latifah Alfahad6Afaf Alsagheir7Afaf Alsagheir8Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaCollege of Medicine, Alfaisal University, Riyadh, Saudi ArabiaCollege of Medicine, Alfaisal University, Riyadh, Saudi ArabiaCollege of Medicine, Alfaisal University, Riyadh, Saudi ArabiaCollege of Medicine, Alfaisal University, Riyadh, Saudi ArabiaDepartment of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaDepartment of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaCollege of Medicine, Alfaisal University, Riyadh, Saudi ArabiaDifferences of sex development (DSD) are a group of congenital conditions involving atypical chromosomal, gonadal, or anatomical sex development. DHX37, a gene involved in ribosome biogenesis, located on chromosome 12, at the 12q24.31 region, has recently emerged as a contributor to 46,XY DSD, particularly gonadal dysgenesis and testicular regression syndrome (TRS). This study presents a case series from Saudi Arabia highlighting novel and known DHX37 variants in three patients with 46,XY DSD. Three Saudi patients presented with ambiguous genitalia, non-palpable or atrophic testes, and hypergonadotropic hypogonadism. Identified variants included two known (p.Arg308Gln, p.Arg674Trp) and one novel (p.Gly478Val) missense mutation. Phenotypic variability ranged from complete testicular regression to partial gonadal dysgenesis. Thus, this is the first case series of DHX37-related DSD in Saudi Arabia, expanding the mutational spectrum and reinforcing the gene’s role in testicular development. Genetic testing, particularly whole-exome sequencing, is essential for accurate diagnosis and management, especially in regions with high consanguinity.https://www.frontiersin.org/articles/10.3389/fendo.2025.1622036/fullDHX37gonadal dysgenesistesticular regression syndromeambiguous genitaliagenetic testingSaudi Arabia |
| spellingShingle | Abeer Alabduljabbar Sara Abid Dania Farooq Sara Aljazaeri Yara Khamag Raghad Alhuthil Latifah Alfahad Afaf Alsagheir Afaf Alsagheir Case Report: De novo DHX37 mutations in Saudi patients with 46,XY differences of sex development Frontiers in Endocrinology DHX37 gonadal dysgenesis testicular regression syndrome ambiguous genitalia genetic testing Saudi Arabia |
| title | Case Report: De novo DHX37 mutations in Saudi patients with 46,XY differences of sex development |
| title_full | Case Report: De novo DHX37 mutations in Saudi patients with 46,XY differences of sex development |
| title_fullStr | Case Report: De novo DHX37 mutations in Saudi patients with 46,XY differences of sex development |
| title_full_unstemmed | Case Report: De novo DHX37 mutations in Saudi patients with 46,XY differences of sex development |
| title_short | Case Report: De novo DHX37 mutations in Saudi patients with 46,XY differences of sex development |
| title_sort | case report de novo dhx37 mutations in saudi patients with 46 xy differences of sex development |
| topic | DHX37 gonadal dysgenesis testicular regression syndrome ambiguous genitalia genetic testing Saudi Arabia |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1622036/full |
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