잠시만 기다려 주세요. 로딩중입니다.

Clinical, endocrinological, and molecular features of four Korean cases of cytochrome P450 oxidoreductase deficiency

Annals of Pediatric Endocrinology & Metabolism 2020년 25권 2호 p.97 ~ 103
이예나, 최진호, 오아름, 김구환, 박숙현, 문정은, 고철우, 전종근, 유한옥,
소속 상세정보
이예나 ( Lee Ye-Na ) - University of Ulsan College of Medicine Asan Medical Center Children’s Hospital Department of Pediatrics
최진호 ( Choi Jin-Ho ) - University of Ulsan College of Medicine Asan Medical Center Children’s Hospital Department of Pediatrics
오아름 ( Oh A-Rum ) - University of Ulsan College of Medicine Asan Medical Center Children’s Hospital Department of Pediatrics
김구환 ( Kim Gu-Hwan ) - University of Ulsan College of Medicine Asan Medical Center Children’s Hospital Medical Genetics Center
박숙현 ( Park Sook-Hyun ) - Kyungpook National University School of Medicine Kyungpook National University Hospital Department of Pediatrics
문정은 ( Moon Jung-Eun ) - Kyungpook National University School of Medicine Kyungpook National University Hospital Department of Pediatrics
고철우 ( Ko Cheol-Woo ) - Kyungpook National University School of Medicine Kyungpook National University Hospital Department of Pediatrics
전종근 ( Cheon Chong-Kun ) - Pusan National University School of Medicine Pusan National University Children’s Hospital Department of Pediatrics
유한옥 ( Yoo Han-Wook ) - University of Ulsan College of Medicine Asan Medical Center Children’s Hospital Department of Pediatrics

Abstract


Purpose: Cytochrome P450 oxidoreductase (POR) deficiency is a rare autosomal recessive disorder caused by mutations in the POR gene encoding an electron donor for all microsomal P450 enzymes. It is characterized by adrenal insufficiency, ambiguous genitalia, maternal virilization during pregnancy, and skeletal dysplasia. In this study, we investigated the clinical, hormonal, and molecular characteristics of patients with POR deficiency in Korea.

Methods: This study included four patients with POR deficiency confirmed by biochemical and molecular analysis of POR. Clinical and biochemical findings were reviewed retrospectively. Mutation analysis of POR was performed by Sanger sequencing after polymerase chain reaction amplification of all coding exons and the exon-intron boundaries.

Results: All patients presented with adrenal insufficiency and ambiguous genitalia regardless of their genetic sex. Two patients harbored homozygous p.R457H mutations in POR and presented with adrenal insufficiency and genital ambiguity without skeletal phenotypes. The other two patients with compound heterozygous mutations of c.[1329_1330insC];[1370G>A] (p.[I444Hfs*6];[R457H]) manifested skeletal abnormalities, such as craniosynostosis and radiohumeral synostosis, suggesting Antley-Bixler syndrome. They also had multiple congenital anomalies involving heart, kidney, and hearing ability. All patients were treated with physiologic doses of oral hydrocortisone.

Conclusions: We report the cases of 4 patients with POR deficiency identified by mutation analysis of POR. Although the study involved a small number of patients, the POR p.R457H mutation was the most common, suggesting founder effect in Korea. POR deficiency is rare and can be misdiagnosed as 21-hydroxylase or 17α-hydroxylase/17,20-lyase deficiency. Therefore, molecular analysis is critical for confirmatory diagnosis.

키워드

Cytochrome P450 oxidoreductase deficiency; Disorders of sex development; POR

원문 및 링크아웃 정보

 

등재저널 정보