In:
Sexual Development, S. Karger AG, Vol. 13, No. 4 ( 2019), p. 178-186
Abstract:
Steroidogenic factor 1 ( 〈 i 〉 NR5A1/SF1 〈 /i 〉 ) is a key transcription factor that is known to regulate the development of adrenal glands and gonads and is also involved in steroidogenesis. Several pathogenic 〈 i 〉 NR5A1 〈 /i 〉 variants have been reported to cause 46,XY disorders of sex development (DSD), with varying clinical phenotypes ranging from hypospadias to complete gonadal dysgenesis. Most often, the primary cause of DSD is due to variants in gene(s) related to gonadal development or the steroidogenic pathway. In the present study, we have analyzed 64 cases of 46,XY DSD for pathogenic 〈 i 〉 NR5A1 〈 /i 〉 variants. We report a total of 3 pathogenic variants of which 2 were novel (p.Gly22Ser and p.Ser143Asn) and 1 was already known (p.Ser32Asn). Functional studies have revealed that the 2 mutations p.Gly22Ser and p.Ser32Asn could significantly affect DNA binding and transactivation abilities. Further, these mutant proteins showed nuclear localization with aggregate formation. The third mutation, p.Ser143Asn, showed unspeckled nuclear localization and normal DNA binding, but the ability of transcriptional activation was significantly reduced. In conclusion, we recommend screening for 〈 i 〉 NR5A1 〈 /i 〉 pathogenic variants in individuals with features of 46,XY DSD for better diagnosis and management.
Type of Medium:
Online Resource
ISSN:
1661-5425
,
1661-5433
Language:
English
Publisher:
S. Karger AG
Publication Date:
2019
detail.hit.zdb_id:
2261528-3
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