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Journal of Assisted Reproduction and Genetics

Erschienen in:

14.01.2020 | Genetics

Functional study of a novel c.630delG (p.Y211Tfs*85) mutation in NR5A1 gene in a Chinese boy with 46,XY disorders of sex development

verfasst von: Sinian Pan, Shili Guo, Liting Liu, Xiaoyuan Yang, Hanmei Liang

Erschienen in: Journal of Assisted Reproduction and Genetics | Ausgabe 2/2020

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Abstract

Purpose

This study aimed to present the clinical features and gene mutation characteristics of a child with 46,XY disorders of sex development (DSD) caused by a novel heterozygous mutation in the NR5A1 gene to determine the potential association between this heterozygous mutation and the pathogenesis of 46,XY DSD.

Methods

We present the case of a Chinese child with ambiguous genitalia at birth but a normal adrenal gland. Targeted next-generation sequencing, comprising 163 candidate genes involved in sexual differentiation and development, was performed, followed by the functional evaluation of the novel NR5A1 mutation.

Result

The patient had a novel heterozygous mutation in the NR5A1 gene, c.630delG (p.Y211Tfs*85). Results revealed that overexpression of p.Y211Tfs*85 impaired steroidogenic factor-1 (SF-1) protein synthesis. Immunofluorescence analysis revealed that both SF-1 wild-type and p.Y211Tfs*85 mutation proteins were localized in the cell nucleus. Furthermore, dual-luciferase reporter assay results revealed that the p.Y211Tfs*85 mutation could effectively downregulate the transcriptional activation of anti-Müllerian hormone and steroidogenic acute regulatory protein genes (P < 0.01). Additionally, the p.Y211Tfs*85 mutation changed three-dimensional conformation of SF-1, and three conformations could be constructed with the mutated amino acid sequences. Therefore, the novel frameshift mutation could result in decreased protein expression of SF-1.

Conclusion

We described a novel mutation in NR5A1 and showed that it might affect protein structure, thereby seriously compromising the role of SF-1 in regulating gonadal development. The novel p.Y211Tfs*85 mutation in the NR5A1 gene enriches the boy of information available regarding the mutation spectrum of this gene in the Chinese population.

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Titel: Functional study of a novel c.630delG (p.Y211Tfs*85) mutation in NR5A1 gene in a Chinese boy with 46,XY disorders of sex development
verfasst von: Sinian Pan
Shili Guo
Liting Liu
Xiaoyuan Yang
Hanmei Liang
Publikationsdatum: 14.01.2020
Verlag: Springer US
Erschienen in: Journal of Assisted Reproduction and Genetics / Ausgabe 2/2020
Print ISSN: 1058-0468
Elektronische ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-019-01676-7

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Functional study of a novel c.630delG (p.Y211Tfs*85) mutation in NR5A1 gene in a Chinese boy with 46,XY disorders of sex development

Abstract

Purpose

Methods

Result

Conclusion

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Abstract

Purpose

Methods

Result

Conclusion

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