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

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*

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

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

METHODSTwo SNPs rs743572 (CYP17 gene 34T/C) and rs9322331 (ERα 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 ERα 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

OBJECTIVETo investigate the relationship between polymorphisms of genes (CYP17, CYP19 and SULT1A1) involved in estrogen metabolism and susceptibility to breast cancer in Chinese women.

METHODSA case-control study was performed. PCR-base restriction fragment length polymorphism (PCR-RFLP) and short tandem repeat polymorphism (STRP) assays were used to detect the polymorphism distribution of CYP17, CYP19 and SULT1A1 in 213 breast cancer cases and 430 matched controls. Logistic regression analyses were used to determine the OR, multivariate adjusted OR and 95% CI of each and all three genes and estrogen exposure factors on the risk of breast cancer. Relationship between polymorphisms and clinic-pathological features was also assessed.

RESULTSThe frequency of A2 allele of CYP17 was 49.8% in cases and 49.1% in controls (P > 0.05). The frequency His allele of SULT1A1 in cases (13.6%) was significant higher than that of controls (9.5%) (P = 0.03). There was also significant difference in the frequencies of (TTTA)10 allele CYP19 which was 12.4% in cases and 8.2% in controls (P = 0.02). Multigenic model indicated that there was an increased risk of breast cancer with more numbers of high-risk genotypes in a dose-response effect (trend P = 0.05). Data from multivariate analysis showed that the allele of SULT1A1 His and CYP19 (TTTA)10 was positively associated with the risk of breast cancer. Other well-established risk factors as higher estrogen exposure including total years of menstrual, early menarche etc, and women with a higher BMI and WHR were all served as independent risks.

CONCLUSIONThis study indicated that the polymorphisms of estrogen-metabolizing genes were related to breast cancer.

Aromatase ; genetics ; Arylsulfotransferase ; genetics ; Breast Neoplasms ; genetics ; Case-Control Studies ; China ; Female ; Genetic Predisposition to Disease ; Humans ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Steroid 17-alpha-Hydroxylase ; genetics

OBJECTIVETo analyze CYP17A1 gene mutations in a child patient with 17 alpha-hydroxylase/17, 20-lyase deficiency (17OHD), and to review characteristics of CYP17A1 gene mutations in Chinese patients with 17OHD.

METHODSClinical data were collected. PCR and DNA sequencing were performed to detect mutations in the patient.

RESULTSThe patient has presented classical features of 17OHD including hypertension, hypokalemia, decreased sex hormones and plasma cortisol, and elevated blood adrenocorticotrophic hormone. A compound heterozygous mutation c.987C>A and c.985del was detected in the CYP17A1 gene, which resulted in two premature stop codons at positions 328 and 417.

CONCLUSIONA compound mutation, c.987C>A and c.985del, has been identified in a patient with 17OHD. Among CYP17A1 gene mutations identified in Chinese patients, missence mutations have been most common, and exons 5 and 8 have been the mutation hotspots.

Adolescent ; Adrenal Hyperplasia, Congenital ; enzymology ; genetics ; Base Sequence ; Female ; Humans ; Lyases ; deficiency ; genetics ; Molecular Sequence Data ; Mutation ; Steroid 17-alpha-Hydroxylase ; genetics

OBJECTIVETo explore the correlation between androgen-related CYP17 gene polymorphisms and female post adolescent acne in Han population in Hunan Province.

METHODSThe female patients with post adolescent acne and high levels of androgen (A group), those without high levels of androgen (B group) and healthy subjects (C group) were enrolled. The CYP17 gene polymorphism was investigated by PCR using DNA samples from peripheral blood lymphocytes. The T-->C transition in the risk allele (A2) produced a new recognition site for the restriction endonuclease MspA1 I. Three genotypes of androgen-related CYP17 gene (A1A1, A1A2, and A2A2) were determined and confirmed by sequencing.

RESULTSThe frequency of the A1A2 gene was similar in the cases and controls (P>0.05). The frequency of A2A2 gene was not significantly different between groups A and C (P>0.05). The frequency of A2A2 gene was significantly different between groups A and B and between groups B and C (P<0.05).

CONCLUSIONThe presence of base substitution in androgen-related CYP17 gene at -34 bp (T-->C) increases the risk of post adolescent acne in female subjects with increased androgen levels.

Acne Vulgaris ; genetics ; Adult ; Androgens ; blood ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Female ; Genotype ; Humans ; Polymorphism, Genetic ; Steroid 17-alpha-Hydroxylase ; genetics

OBJECTIVETo investigate the association between the polymorphism of CYP17 gene and risk of prostate cancer in Chinese Vigurs men.

METHODSA case-control study including 31 patients with prostate cancer and 104 aged-matched controls was conducted. The polymorphism was investigated by PCR using DNA from peripheral blood lymphocytes. The transition (T-->C) in the risk allele (A2) produced a new recognition site for the restriction enzyme MSPAI I. Three genotypes of CYP17 gene (A1/A1, A1/A2, A2/A2) were determined and confirmed by sequencing.

RESULTSCompared with male A1/A1 genotype, the odds ratios were 1.49 and 2.87 for the A1/A2 and A2/A2 genotypes (P =0.321, 0. 052, respectively). Comparison among 3 subgroups (division by genetypes) of prostate cancer patients, the PSA levels were not significantly different. But in the controls, PSA levels in A1/A2 group were higher but not significant than those in A1/A1 group (P = 0.062). Then, PSA levels in A2/A2 group were significantly higher than those A1/ A1 group (P = 0.018).

CONCLUSIONMore frequency of A2/A2 genotype in prostate cancer than in the control may be associated with the morbidity of prostate cancer in Vigurs male population. Meanwhile, the significant high PSA levels in A2/A2 group also support the view.

Aged ; Aged, 80 and over ; Case-Control Studies ; China ; ethnology ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Prostatic Neoplasms ; ethnology ; genetics ; Steroid 17-alpha-Hydroxylase ; genetics

OBJECTIVETo detect CYP17A1 gene mutation in a patient with 17 alpha-hydroxylase/17, 20-lyase deficiency and her family members.

METHODGenomic DNA was extracted from the blood of the patient, her parents and twin sister. The 8 exons of CYP17A1 gene were amplified with polymerase chain reaction (PCR) and screened for mutations by sequencing.

RESULTThe analysis revealed that the patient was a compound heterozygote carrying two different inherited point mutations on CYP17A1 gene. They were nt186delC on exon 1 and nt1085G > A on exon 6. This type of mutation could induce 17OHD because of complete loss of 17 alpha-hydroxylase activities. And her parents and the twin sister were carriers on CYP17A1 gene. In addition, the mutation nt186delC was a novel point mutation and it was not discovered in normal children.

CONCLUSIONA new compound heterozygote carrying two different inherited point mutations on CYP17A1 gene was found, and her parents and twin sister were carriers. This is probably the first report in the world of a twin sisters of whom one is a patient with 17OHD and the other is a carrier of CYP17A1 gene mutation.

Adrenal Hyperplasia, Congenital ; genetics ; Child ; DNA Mutational Analysis ; Exons ; Female ; Heterozygote ; Humans ; Male ; Pedigree ; Point Mutation ; Steroid 17-alpha-Hydroxylase ; genetics

OBJECTIVETo investigate the association between polymorphism of CYP17 gene and serum hormone concentrations in aged men.

METHODSEighty-three healthy men at the average age of 66.7 were divided into a < 66.7 group (n = 36) and a > 66.7 group (n = 47), and the polymorphism of CYP17 gene in the 5' promoter region was investigated by PCR using DNA from the men's peripheral blood lymphocytes. A new recognition site was created for the restriction enzyme MspA1 I by transition (T --> C) in the risk allele (A2). Three genotypes A1/A1, A1/A2, A2/A2 were established, serum sex-hormone levels measured, and mean hormone concentration evaluated in each genotype and age group.

RESULTSNo evidence was found that the testosterone (T) level, estrogen (E2) level and T/E2 ratio were associated with the genotype of CYP17 gene. There was no significant difference in T and E2 levels between the two groups, but there was a significant increase in the T/E2 ratio (P < 0.05).

CONCLUSIONA2 allele does not increase sex hormone levels in aged men, but the T/E, ratio was higher in the > 66.7 group than in the < 66.7 group. This may be closely associated with the mechanism of benign prostate hyperplasia and prostate cancer in aged men.

Adult ; Aged ; Aged, 80 and over ; Estradiol ; blood ; Genotype ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Promoter Regions, Genetic ; genetics ; Steroid 17-alpha-Hydroxylase ; genetics ; Testosterone ; blood