Sequenzierung des NR5A1-Genlokus bei Patienten mit Besonderheiten der Geschlechtsentwicklung unklarer Ursache

The NR5A1 gene encoding the steroidogenic factor-1 is a critical factor involved in testis development and a mutation in this gene can cause gonadal dysgenesis with or without adrenal insufficiency in 46,XY individuals. Such a condition can be distinguished from Androgen insensitivity syndrim (AIS), which is characterized by the resistance of the androgen receptor (AR) to male steroid hormones due to a mutation in the AR gene. The clinical phenotypes of individuals with AIS range from external genitalia being completely or partially masculinized to completely female genitalia. An undervirilization can manifest for example in micropenis, bifid scrotum, cryptorchism, hypospadia, labial fusion, and clitoromegaly. AIS Type II has the same range of clinical features but is characterized by reduced AR-activity despite the lack of AR coding gene mutations. Previous studies indicate that patients who were diagnosed with AIS due to their clinical features and hormone levels but lacking AR gene mutations may in fact have a mutation in the NR5A1 gene.

The purpose of this study was to identify mutations in the NR5A1 gene in patients with 46,XY DSD of unknown etiology and in patients with AIS Type II.

Sanger Sequencing and NGS of the NR5A1 coding sequence from exon 1 to exon 7 was performed. Available patient data was collected, including detailed physical examination of the patient and its genitalia, measurements of hormone levels, diagnostics, and surgeries.

This study identified seven heterozygous NR5A1 mutations causing variable clinical features. Conclusively, AIS patients who do not harbor any mutation and patients with 46,XY DSD of unknown etiology should be screened for NR5A1 mutations.


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