ESPE2021 ePoster Category 2 Sex differentiation, gonads and gynaecology or sex endocrinology (52 abstracts)
A case of gender developmental disorder with difficulty in molecular diagnosis: New variant in NR5A1 gene
Emrullah Arslan 1 , Aslı Ece Solmaz 2 , Ayca Aykut 2 , Asude Durmaz 2 , Tahir Atik 3 , Damla Goksen 1 , Ibrahim Ulman 4 , Burcu Ozbaran 5 , Samim Ozen 1 & Sukran Darcan 1
1Ege Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, Izmir, Turkey; 2Ege Faculty of Medicine, Department of Medical Genetics, Izmir, Turkey; 3Ege Faculty of Medicine, Department of Pediatric Genetics, Izmir, Turkey; 4Ege Faculty of Medicine, Pediatrics Urology Surgery, Izmir, Turkey; 5Ege Faculty of Medicine, Department of Child and Adolescent Pschiatry, Izmir, Turkey
"Steroidogenic Factor-1" (SF-1); It is encoded by the NR5A1 gene in 9q 33.3 and regulates the transcription of genes involved in steroidogenesis. It is reported that 46 of the variants in this gene constitute 10-20% of XY sex development disorders (DSD). The patient admitted because of a swelling in the left groin at one month old. She was raised as female. Uterus was 12x2.5 mm in ultrasonography and the gonad in the inguinal region was evaluated as testis. She was Prader stage 3, single opening, phallus 1 cm, bilateral 0.5x0.5cm ovoid gonads were palpated in the inguinal region. Laboratory values were FSH: 8.99 mIU/ml (N: 0.16- 4.1), AMH: 16.59 ng/ml (N: 39.1 -91.1) Total testesterone: 50 ng/dl (N: 60 – 400). Serum electrolytes, glucose, ACTH, DHEA-S, 17-0H Progesterone were normal. hCG stimulation test was unresponsive. She was SRY (+) and XY was detected by QF-PCR. Male urethra, utriculus, and ureter orifices were observed in cystoscopic examination. With an initial diagnosis of partial gonadal dysgenesis; no mutation was found with the targeted Next-Generation Sequence (NGS) analysis (Trusight One) panel. The gender development disorder council decided to raise the patient as a male with the parents. Her identity was changed at the age of 1 year and corrective operations were performed. Heterozygous c.1161_1232delinsGGTGACAAATAAGCAG (p. His387GlnfsTer161) variant was found in the repeated analysis of the NR5A1 gene with Sanger sequence analysis of the patient, who was thought to have SF-1 deficiency clinically. It has been shown that the variant, defined as de novo, can disrupt the protein structure with modeling programs and is pathogenic according to ACGM criteria. Mutations in NR5A1 can appear in a wide spectrum from hypospadias, uncertain external genital structure, anorchia, gonadal dysgenesis to infertility, and completely female external genital structure. Detecting 'indel' mutations with analysis programs is still a challenging field in next generation sequence analysis. Especially variants greater than 20bp and heterozygous as in this case increase the possibility of giving false negative results in the targeted new generation sequence analysis analysis. In 46, XY DSD cases, even if molecular diagnosis is not made in the targeted NGS panel, repeating the molecular genetic analysis with Sanger sequence analysis in case of clinical strong suspicion may be necessary to make a diagnosis.
Article tools
My recent searches
My recently viewed abstracts
Authors
ESPE Abstracts
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more