OBJECTIVE: To identify pathogenic variants in 5 sporadic patients and two Chinese pedigrees affected with 17-hydroxylase deficiency (17-OHD). METHODS: Peripheral blood samples were collected with informed consent. Variants of CYP17A1 gene were screened by PCR and Sanger sequencing. Suspected mutations were validated in other members of the pedigrees. RESULTS: Gene sequencing has identified a homozygous c.985_987delTACinsAA (Y329Kfs) mutation in exon 6 of the CYP17A1 gene in 4 patients and the sister of case 3. Case 1 was found to harbor compound heterozygous mutations c.1459_1467del9 (p.D487_F489del) and c.1244-3C>A. The parents and brother of cases 2 and 5 were heterozygous carriers of a c.985_987delTACinsAA(Y329Kfs) mutation. CONCLUSION Mutations of the CYP17A1 gene probably underlie the pathogenesis of 17-OHD, for which c.985_987delTACinsAA(Y329Kfs) is the most common. The c.1244-3C>A is a novel mutation. Above results have facilitated genetic counseling for the affected families.
Adrenal Hyperplasia, Congenital ; genetics ; Exons ; Female ; Humans ; Male ; Mutation ; Pedigree ; Steroid 17-alpha-Hydroxylase ; genetics

OBJECTIVE: To investigate whether polymorphism of CYP17 gene is associated with the risk of advanced endometriosis in Korean women. METHODS: The 194 endometriosis patients and 209 controls were enrolled. Blood samples were collected from 194 patients with endometriosis stages III and IV diagnosed by both pathologic and laparoscopic findings. The women undergoing laparoscopic surgery or laparotomy for non-malignant lesions were included in the control group. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) of PCR products were done to determine all individuals' genotype. RESULTS: The heterozygous allele in CYP17 gene was most common genotypes in both endometriosis and healthy control groups (54.6% vs. 38.8%). In women with heterozygous A1/A2 genotype, there was increased endometriosis risk and this difference was statistically significant (p<0.05). CONCLUSION: The results suggest that the CYP17 genetic polymorphism might be associated with advanced endometriosis risk in Korean women.
Alleles ; Endometriosis* ; Female ; Genotype ; Humans ; Laparoscopy ; Laparotomy ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Steroid 17-alpha-Hydroxylase*

CYP21A2 gene mutations in a child with congenital adrenal hyperplasia (CAH), and the child's parents, were detected in the study. The clinical features, treatment monitoring and molecular genetic mechanism of CAH are reviewed. In the study, DNA was extracted from peripheral blood samples using the QIAGEN Blood DNA Mini Kit; a highly specific PCR primer for CYP21A2 gene was designed according to the sequence difference between CYP2lA2 gene and its pseudogene; the whole CYP2lA2 gene was amplified with PrimeSTAR DNA polymerase (Takara), and the amplification product was directly sequenced to detect and analyze CYP2lA2 gene mutation. The child was clinically diagnosed with CAH (21-hydroxylase deficiency, 21-OHD) at the age of 36 days, and the case was confirmed by genetic diagnosis at the age of 1.5 years. The proband had a homozygous mutation at c.293-13C in the second intron of CYP21 gene, while the parents had heterozygous mutations. Early diagnosis and standard treatment of CAH (21-OHD) should be performed to prevent salt-wasting crisis and reduce mortality; bone aging should be avoided to increase final adult height (FAH), and reproductive dysfunction due to oligospermia in adulthood should be avoided. These factors are helpful for improving prognosis and increasing FAH. Investigating the molecular genetic mechanism of CAH can improve recognition and optimize diagnosis of this disease. In addition, carrier diagnosis and genetic counseling for the proband family are of great significance.
17-alpha-Hydroxyprogesterone ; blood ; Adrenal Hyperplasia, Congenital ; blood ; genetics ; Humans ; Infant ; Male ; Mutation ; Steroid 21-Hydroxylase ; genetics

Objective To analyze the clinical features of 17&alpha;-hydroxylase deficiency and explore the appropriate timing and methods of surgical treatment. Methods We retrospectively analyzed the clinical data of patients with complete 17&alpha;-hydroxylase deficiency,containing Y chromosome material in their karyotype,adimitted to Peking Union Medical College Hospital from January 2004 to December 2014. Results Thirty patients with complete 17&alpha;-hydroxylase deficiency were included. Their social gender were all female and the mean age at diagnosis was (16.1±2.7) years. Twenty-six patients (86.7%) presented with primary amenorrhea and hypertension. The development of secondary sexual characteristics was poor and their uterus was absent. The levels of gonadotropin,progesterone,and adrenocorticotropic hormone were elevated in all patients and the levels of estradiol,testosterone,and cortisol were decreased. All patients had undergone laparoscopic gonadectomy. Most (86.7%) of the gonads were located in abdomen,while 13.3% were in inguinal canal. Histopathology confirmed that gonadal malignancy was obsetved in two patients (6.7%): one with leydig cell tumor and the other with sertoli cell tumor. Conclusions Patients with complete 17&alpha;-hydroxylase deficiency have specific clinical features. Early diagnosis and timely laparoscopic gonadectomy are critical to prevent gonadal malignancy.
Adolescent ; Adrenal Hyperplasia, Congenital ; complications ; surgery ; Amenorrhea ; etiology ; Female ; Humans ; Hypertension ; etiology ; Karyotyping ; Retrospective Studies ; Steroid 17-alpha-Hydroxylase

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder, and 17α-hydroxylase deficiency (17α-OHD) is a rare type of CAH. 17α-OHD is caused by CYP17 gene mutation, resulting in partial or complete deficiency of 17α-hydroxylase, which in turn leads to the lack of cortisol and sex hormone production. The disease is manifested by excessive secretion of adrenocorticotropic hormone (ACTH), decreased levels of estradiol (E2) and androgen, elevated levels of proges-terone (P), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Most of the patients are female in gender. According to the chromosome karyotype, 17α-OHD can be divided into 46XX and 46XY, of which 46XX is rarer. The clinical manifestations are hypokalemia and hypertension. Patients with 46XX-karyotype may have irregular menstruation, amenorrhea, and infertility. The severity of symptoms varies according to the degree of 17α-hydroxylase deficiency. Due to its untypical manifestation, the patients with partial 17α-OHD are more likely to be missed or misdiagnosed. Some 17α-OHD patients with 46, XX karyotypes have different degrees of development of internal and external reproductive organ and spontaneous menstrual cycle, so they may have the potential ovulation and fertility opportunities. However, due to the adverse effects of high serum P level on the endometrium, the patients would have infertility problems. To date, four cases from foreign countries have been reported about the infertility treatments among 46XX-17α-OHD patients, and two cases were mentioned in China without describing the process of treatments. Here, one case with partial 46XX-17α-OHD was diagnosed and successfully conceived and delivered after in vitro fertilization-embryo transfer (IVF-ET) in the Center for Reproductive Medicine, Peking University Third Hospital. Controlled ovarian stimulation with ultra-long protocol was initiated after glucocorticoid therapy was given to reduce P level. Ten oocytes were obtained and 6 embryos were cryopreserved. Frozen-thawed embryo transfer under hormonal replacement after gonadotropin releasing hormone agonist (GnRH-a) was carried out in an artificial cycle, and then the patient was successfully pregnant and delivered a healthy boy after 37 weeks of gestation by cesarean section. The treatment of this case suggests that patients with partial 46XX-17α-OHD can obtain oocytes and embryos with good quality. IVF combined with frozen-thawed embryo transfer under artificial cycle is an effective method for patients with partial 46XX-17α-OHD with infertility.
Adrenal Hyperplasia, Congenital/genetics* ; Cesarean Section ; Embryo Transfer ; Female ; Humans ; Infertility ; Male ; Pregnancy ; Steroid 17-alpha-Hydroxylase/genetics*

OBJECTIVETo investigate the association of single nucleotide polymorphisms in cytochrome P450 17 (CYP17) and estrogen receptor alpha (ER&alpha; ) genes with the risk of endometriosis among southern Chinese women.

METHODSTwo SNPs rs743572 (CYP17 gene 34T/C) and rs9322331 (ER&alpha; gene -397T/C) were genotyped by high resolution melting curve in 432 endometriosis patients and 499 matched controls.

RESULTSThere was no significant difference in the genotype frequencies of the two loci between endometriosis patients and the control subjects (P> 0.05). And there was no significant interaction effect of these two genes on the disease either.

CONCLUSIONCYP17 gene and ER&alpha; gene may not be genetic risk factors for endometriosis among southern women in China.

Asian Continental Ancestry Group ; genetics ; Endometriosis ; genetics ; Estrogen Receptor alpha ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Risk Factors ; Steroid 17-alpha-Hydroxylase ; genetics

17alpha-hydroxylase and 17,20-lyase are enzymes encoded by the CYP17A1 gene and are required for the synthesis of sex steroids and cortisol. In 17alpha-hydroxylase deficiency, there are low blood levels of estrogens, androgens, and cortisol, and resultant compensatory increases in adrenocorticotrophic hormone that stimulate the production of 11-deoxycorticosterone and corticosterone. In turn, the excessive levels of mineralocorticoids lead to volume expansion and hypertension. Females with 17alpha-hydroxylase deficiency are characterized by primary amenorrhea and delayed puberty, with accompanying hypertension. Affected males usually have female external genitalia, a blind vagina, and intra-abdominal testes. The treatment of this disorder is centered on glucocorticoid and sex steroid replacement. In patients with 17alpha-hydroxylase deficiency who are being raised as females, estrogen should be supplemented, while genetically female patients with a uterus should also receive progesterone supplementation. Here, we report a case of a 21-year-old female with 17alpha-hydroxylase deficiency who had received inadequate treatment for a prolonged period of time. We also include a brief review of the recent literature on this disorder.
Adrenocorticotropic Hormone ; Amenorrhea ; Androgens ; Corticosterone ; Estrogens ; Female ; Genitalia ; Humans ; Hydrocortisone ; Hypertension ; Male ; Mineralocorticoids ; Progesterone ; Puberty, Delayed ; Steroid 17-alpha-Hydroxylase* ; Steroids ; Testis ; Uterus ; Vagina ; Young Adult

PURPOSE: Cytochrome P450 17alpha-hydroxylase/17,20-lyase (CYP17A1) is a key enzyme in the androgen biosynthesis pathway. CYP17A1 has been focused on because of the promising results of a potent CYP17A1 inhibitor in the treatment of castration-resistant prostate cancer (CRPC). A hypothesis that intratumoral androgenesis may play a role in the progression of CRPC has recently been postulated. Thus, we evaluated whether commonly used prostate cancer cell lines express CYP17A1. MATERIALS AND METHODS: Androgen-sensitive LNCaP and androgen-insensitive PC-3 and DU145 cells were used. To evaluate the expression of CYP17A1 protein and RNA, we performed Western blotting and RT-PCR, respectively. RESULTS: We were unable to detect either CYP17A1 protein or RNA in any of the cell lines tested. We failed to detect any expression of CYP17A1, despite several repetitions of these techniques under different conditions. CONCLUSIONS: The expression of CYP17A1 protein and RNA in LNCaP, PC-3, and DU145 cells appears to be either absent or too low for detection. The mechanism of action of abiraterone acetate, a CYP17A1 inhibitor, may be related more to adrenal androgen blockade than to intratumoral androgenesis.
Androgens ; Androstadienes ; Blotting, Western ; Cell Line ; Cytochrome P-450 Enzyme System ; Cytochromes ; Prostate ; Prostatic Neoplasms ; RNA ; Steroid 17-alpha-Hydroxylase ; Abiraterone Acetate

BACKGROUND: High levels of 17-hydroxyprogesterone (17-OHP) are frequently observed in premature infants without congenital adrenal hyperplasia. The purpose of this study is to set cut-off limits of 17-OHP on the basis of gestational age at birth and birth weight. METHODS: Blood spot 17-OHP concentrations were measured in 1,000 infants on the 3th day of life at Inha University Hospital. An enzyme-linked immunosorbent assay (ELISA) method (ICN Neoscreen ELISA 17-hydroxyprogesterone kit, ICN Pharmaceuticals. Inc., Japan) was used. The values obtained were analyzed with respect to birth weight and gestational age at birth in order to decide the appropriate cut-off limits in a neonatal mass screening for 21-hydroxylase deficiency. RESULTS: In the neonatal mass screening for CAH, the cut-off limits for determining the 17-OHP for recall, were decided as follows: (1) 57.65, 39.88, 33.52 ng/mL for gestational age at birth of 35 weeks or less, 36-37, and 38 weeks or more, respectively, and (2) 54.88, 43.86, 32.92 ng/mL for birth weight of 2.49 or less, 2.50-2.99, 3.00 kg or more, respectively. CONCLUSIONS: The cut-off limits on the basis of gestational age at birth and birth weight should be used in the screening for congenital adrenal hyperplasia. We believe that the false positive rate in premature infants can be reduced using this method.
17-alpha-Hydroxyprogesterone* ; Adrenal Hyperplasia, Congenital ; Birth Weight* ; Enzyme-Linked Immunosorbent Assay ; Gestational Age* ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Mass Screening ; Neonatal Screening ; Parturition* ; Steroid 21-Hydroxylase

OBJECTIVE: To investigate whether polymorphism of CYP17 gene is associated with the risk of polycystic ovary syndrome (PCOS) in Korean women. METHODS: The 86 PCOS patients and 75 controls were enrolled. Blood samples were collected from 86 patients diagnosed according to the 2003 revised criteria of the Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Age matched women with regular menstruation from same geographic region were recruited on the control subject. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) of PCR products were done to determine all individuals' genotype. RESULTS: In women with A1A1 genotype, there was increased PCOS risk and this difference was statistically significant (OR 2.2 (CI 1-4.7)). CONCLUSION: The results suggest that the CYP17 A1A1 genetic polymorphism might be associated with PCOS risk in Korean women.
Consensus Development Conferences as Topic ; Female ; Genotype ; Humans ; Menstruation ; Polycystic Ovary Syndrome ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Steroid 17-alpha-Hydroxylase*