Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
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Cholesterol side-chain cleavage enzyme deficiency caused by a novel homozygous variant in P450 sidechain cleavage enzyme gene (CYP11A1) in a 46,XX Korean girl

  • Ye Ji Kim (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Sun Cho (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Hwa Young Kim (Department of Pediatrics, Seoul National University Bundang Hospital) ;
  • Young Hwa Jung (Department of Pediatrics, Seoul National University Bundang Hospital) ;
  • Jung Min Ko (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Chang Won Choi (Department of Pediatrics, Seoul National University Bundang Hospital) ;
  • Jaehyun Kim (Department of Pediatrics, Seoul National University Bundang Hospital)
  • Received : 2023.03.26
  • Accepted : 2023.05.28
  • Published : 2023.06.30
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Abstract

The CYP11A1 gene encodes for the cholesterol side-chain cleavage enzyme (P450scc), which initiates steroid hormone biosynthesis. Defective P450scc activity results in severe glucocorticoid and mineralocorticoid deficiencies. We describe a case of P450scc deficiency due to a novel homozygous CYP11A1 variant inherited from the mother with a possibility of uniparental disomy (UPD). The patient was a female, had no family history of endocrine disease, and showed adrenal insufficiency at 13 days of age. Hormonal analysis with an adrenocorticotropic hormone stimulation test showed both glucocorticoid and mineralocorticoid deficiencies, presumed to be a defect of the early stage of steroidogenesis. Exome sequencing reported a novel homozygous frameshift variant of CYP11A1 (c.284_285del, p.Asn95Serfs*10), which was inherited from the mother. Additionally, homozygosity in 15q22.31q26.2, which included CYP11A1, was identified using a chromosomal microarray. It was suggested that the possibility of maternal UPD was involved as the cause of a P450scc deficiency by unmasking the maternally derived affected allele. To our understanding, P450scc deficiency associated with UPD encompassing CYP11A1 had not been reported in Korea before. Genetic analysis can help diagnose rare causes of primary adrenal insufficiency, including P450scc deficiency.

Keywords

Acknowledgement

The authors thank the patient and her parents, who consigned to participate in this report.

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