Clinical and genetic analysis of cytochrome P450 oxidoreductase (POR) deficiency in a female and the analysis of a novel POR intron mutation causing alternative mRNA splicing: Overall analysis of a female with POR deficiency
| Autor: | Bo Huang, Wei Yang, Guijin Zhu, Lei Jin, Tao Zhang, Xinling Ren, Zhou Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Mutant Biology Gene mutation Compound heterozygosity medicine.disease_cause 03 medical and health sciences Exon 0302 clinical medicine Cytochrome P-450 Enzyme System medicine Genetics Humans Genetic Testing Gene Genetics (clinical) Mutation 030219 obstetrics & reproductive medicine Base Sequence Alternative splicing Obstetrics and Gynecology General Medicine Exons POR Deficiency Molecular biology Introns Alternative Splicing 030104 developmental biology Reproductive Medicine Female Antley-Bixler Syndrome Phenotype Developmental Biology |
| Zdroj: | J Assist Reprod Genet |
| Popis: | OBJECTIVE: To characterize the clinical features of a female with P450 oxidoreductase (POR) deficiency and to investigate the underlying mechanisms of POR inactivation. METHODS: The proband was a 35-year-old woman with primary infertility and menstrual irregularity. The reproductive endocrine profile was evaluated. DNA sequencing was conducted for the identification of POR gene mutation. RT-PCR was performed to confirm the impact of the mutation on POR mRNA. A molecular model was built for the structural analysis of mutant POR protein. RESULTS: The evaluation of reproductive endocrine profile revealed elevation of serum follicle-stimulating hormone (11.48 mIU/ml), progesterone (11.00 ng/ml), 17α-hydroxyprogesterone (24.24 nmol/l), dehydroepiandrosterone (6300 nmol/l), and androstenedione (3.89 nmol/l) and decreased estradiol (36.02 pg/ml). Sequencing of the POR gene showed the female was a compound heterozygote of the paternal P399_E401 deletion and a novel maternal IVS14-1G>C mutation. Functional analysis revealed IVS14-1G>C mutation caused alternative splicing of POR mRNA, with the loss of 12 nucleotides in exon 15 (c.1898_1909delGTCTACGTCCAG). Also, the resulting mutant POR protein had a V603_Q606 deletion, which inactivated the nucleotide-binding domain of NADPH in POR protein (K602_Q606). CONCLUSION: The mutation IVS14-1G>C of the POR gene could cause alternative splicing of POR mRNA and dysfunction of the resulting POR protein. Under proper IVF strategy with glucocorticoid therapy and endometrial preparation, females with mild POR deficiency still have the opportunity to have a live birth. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|