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Novel compound heterozygous mutations in the desert hedgehog (DHH) gene in cases of siblings with 46,XY disorders of sexual development
BACKGROUND: Disorders of sex development (DSD) are congenital disorders in which the development of the chromosomal, gonadal, or anatomical sex is atypical. Mutations in various genes can impede gonadal development, hormone synthesis, or hormone function and cause DSD. METHODS: Exome sequencing was...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377103/ https://www.ncbi.nlm.nih.gov/pubmed/35971145 http://dx.doi.org/10.1186/s12920-022-01334-5 |
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author | Wei, Jia Wu, Jiaqi Ru, Wei Chen, Guangjie Gao, Lei Tang, Daxing |
author_facet | Wei, Jia Wu, Jiaqi Ru, Wei Chen, Guangjie Gao, Lei Tang, Daxing |
author_sort | Wei, Jia |
collection | PubMed |
description | BACKGROUND: Disorders of sex development (DSD) are congenital disorders in which the development of the chromosomal, gonadal, or anatomical sex is atypical. Mutations in various genes can impede gonadal development, hormone synthesis, or hormone function and cause DSD. METHODS: Exome sequencing was performed for two siblings with 46,XY DSD. All mutations identified by exome sequencing were confirmed by Sanger sequencing. RESULTS: The 13-month-old younger sibling had a female appearance of the external genital with a clitoris that was assessed as Prader III and scored 2 in the external masculinization score evaluative test. The 16-year-old elder sibling had severe hypospadias. Exome sequencing revealed compound heterozygous mutations in exon 3 of DHH in the siblings with 46,XY DSD. The frameshift mutation (NM_021044.3: c.602delC) was derived from the father and was predicted to be deleterious. The (c.937G > T) substitution mutation was derived from the mother. CONCLUSIONS: Novel compound heterozygous mutations of DHH led to 46,XY DSD in two siblings. This study expands the phenotypic mutation spectra of DHH in patients with 46,XY DSD. |
format | Online Article Text |
id | pubmed-9377103 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-93771032022-08-16 Novel compound heterozygous mutations in the desert hedgehog (DHH) gene in cases of siblings with 46,XY disorders of sexual development Wei, Jia Wu, Jiaqi Ru, Wei Chen, Guangjie Gao, Lei Tang, Daxing BMC Med Genomics Research Article BACKGROUND: Disorders of sex development (DSD) are congenital disorders in which the development of the chromosomal, gonadal, or anatomical sex is atypical. Mutations in various genes can impede gonadal development, hormone synthesis, or hormone function and cause DSD. METHODS: Exome sequencing was performed for two siblings with 46,XY DSD. All mutations identified by exome sequencing were confirmed by Sanger sequencing. RESULTS: The 13-month-old younger sibling had a female appearance of the external genital with a clitoris that was assessed as Prader III and scored 2 in the external masculinization score evaluative test. The 16-year-old elder sibling had severe hypospadias. Exome sequencing revealed compound heterozygous mutations in exon 3 of DHH in the siblings with 46,XY DSD. The frameshift mutation (NM_021044.3: c.602delC) was derived from the father and was predicted to be deleterious. The (c.937G > T) substitution mutation was derived from the mother. CONCLUSIONS: Novel compound heterozygous mutations of DHH led to 46,XY DSD in two siblings. This study expands the phenotypic mutation spectra of DHH in patients with 46,XY DSD. BioMed Central 2022-08-15 /pmc/articles/PMC9377103/ /pubmed/35971145 http://dx.doi.org/10.1186/s12920-022-01334-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Wei, Jia Wu, Jiaqi Ru, Wei Chen, Guangjie Gao, Lei Tang, Daxing Novel compound heterozygous mutations in the desert hedgehog (DHH) gene in cases of siblings with 46,XY disorders of sexual development |
title | Novel compound heterozygous mutations in the desert hedgehog (DHH) gene in cases of siblings with 46,XY disorders of sexual development |
title_full | Novel compound heterozygous mutations in the desert hedgehog (DHH) gene in cases of siblings with 46,XY disorders of sexual development |
title_fullStr | Novel compound heterozygous mutations in the desert hedgehog (DHH) gene in cases of siblings with 46,XY disorders of sexual development |
title_full_unstemmed | Novel compound heterozygous mutations in the desert hedgehog (DHH) gene in cases of siblings with 46,XY disorders of sexual development |
title_short | Novel compound heterozygous mutations in the desert hedgehog (DHH) gene in cases of siblings with 46,XY disorders of sexual development |
title_sort | novel compound heterozygous mutations in the desert hedgehog (dhh) gene in cases of siblings with 46,xy disorders of sexual development |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377103/ https://www.ncbi.nlm.nih.gov/pubmed/35971145 http://dx.doi.org/10.1186/s12920-022-01334-5 |
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