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J Pediatr Genet
DOI: 10.1055/s-0043-1764480
Original Article

A Novel NR5A1 Mutation in a Thai Boy with 46, XY DSD

Suttipong Wacharasindhu 
1   Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
,
Chupong Ittiwut
2   Central Laboratory, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
,
Rungnapa Ittiwut
3   Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
4   Department of Pediatrics, Center of Excellence for Medical Genomics, Medical Genomics Cluster, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
,
Suphab Aroonparkmongkol
1   Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
,
Kanya Suphapeetiporn
3   Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
4   Department of Pediatrics, Center of Excellence for Medical Genomics, Medical Genomics Cluster, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
› Author Affiliations Funding This work was supported by the Rachadapiseksompotch Fund (RA 59/008), Faculty of Medicine, Chulalongkorn University.
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Abstract

Disorders of sex development (DSD) can be classified as 46,XX DSD, 46,XY DSD, and sex chromosome DSD. Several underlying causes including associated genes have been reported. Steroidogenic factor-1 is encoded by the NR5A1 gene, a crucial regulator of steroidogenesis in the growth of the adrenal and gonadal tissues. It has been discovered to be responsible for 10 to 20% of 46, XY DSD cases. Here, we described a 2-month-old infant who had ambiguous genitalia and 46, XY. Using whole exome sequencing followed by polymerase chain reaction–Sanger sequencing, a novel heterozygous nonsense c.1249C > T (p.Gln417Ter) variant in the NR5A1 gene was identified. It is present in his mother but absent in his father and maternal aunt and uncle. At the age of 7 months, the patient received a monthly intramuscular injection of low-dose testosterone for 3 months in a row. His penile length and diameter increased from 1.8 to 3 cm and from 0.8 to 1.3 cm, respectively. The patient also had normal adrenal reserve function by adrenocorticotropic hormone stimulation test. This study identified a novel causative p.Q417X (c.1249C > T) variant in NR5A1 causing 46,XY DSD in a Thai boy which is inherited from his unaffected mother.

Keywords

disorders of sex development - NR5A1 - novel - mutation


Publication History

Received: 06 July 2022

Accepted: 13 February 2023

Article published online:
20 March 2023

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