Work

Compound heterozygous variants in POR gene identified by whole‐exome sequencing in a Chinese pedigree with cytochrome P450 oxidoreductase deficiency

Year: 2018

Type: article

Abstract: Importance Cytochrome P450 oxidoreductase deficiency (PORD) is a rare disease exhibiting a variety of clinical manifestations. This condition specifically leads to disordered steroidogenesis, which can affect the development of the reproductive system, skeleton, and other parts of the body. The severe form of PORD is difficult to differentiate with Antley‐Bixler syndrome (ABS). The genetic characters and clinical evaluation of PORD are still unclear in China. Objective To perform an exome analysis and identify the pathogenic cause in order to assist clinicians to obtain a proper evaluation on the genetic condition. Methods The proband underwent detailed physical evaluations. DNA of the proband and his parents was isolated and whole‐exome sequencing (WES) was performed. Variants were analyzed and evaluation according to the ACMG guideline. Results A 1‐year‐old Chinese boy with midface hypoplasia, choanal stenosis, multiple joint contractures, micropenis and right cryptorchidism was misdiagnosed with Crouzon syndrome. By trio‐whole‐exome sequencing, we identified an unreported compound heterozygous mutation (c.667C>T, p.R223* and c.1370G>A, p.R457H) in POR in the proband. This mutation was inherited from healthy heterozygous parents, supporting the diagnosis of PORD, which was further confirmed by biochemical characteristics. Interpretation We have identified a pathogenic variant with an unreported compound heterozygous POR mutation, which expands the clinical and genetic spectra of PORD and emphasizes the usefulness of WES for genetic diagnosis.

Source: Pediatric Investigation

DOI: 10.1002/ped4.12035

Authors: Chanjuan Hao, Jun Guo, Ruolan Guo, Zhan Qi, Wei Li, Xin Ni

Institutions: Capital Medical University, Beijing Children’s Hospital

Language: English

Topic: Genomics and Rare Diseases

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,000