“…The T318 M mutation is most common among Yemenis [ 2 , 27 , 28 ], and some new mutations such as c.53_54insT, G206 V, W260X, R448P, and H465L are often found in Saudi Arabs [ 29 – 31 ]. The R454C mutation has only been reported among the Chinese [ 8 , 10 , 32 ]. Fig.…”
Background11β-hydroxylase deficiency (11OHD) is extremely rare, and reports of non-classical 11OHD are even rarer. Non-classical 11OHD usually presents as premature adrenarche, hyperandrogenism, menstrual disorders, and hypertension. Because the symptoms of non-classical 11OHD are mild, delayed diagnosis or misdiagnosis as polycystic ovary syndrome or primary hypertension is common.Case presentationThis paper introduces a case of a young female patient presenting hypertension and menstrual disorders. Laboratory examination revealed increased androgen levels, mild adrenal hyperplasia, mild left ventricular hypertrophy, and mild sclerosis of the lower limb arteries. 11OHD was confirmed by genetic testing, and the patient was found to carry compound heterozygous mutations in CYP11B1 (c.583 T > C and c.1358G > A). The mutation Y195H is located in exon 3 and has not been reported previously. In silico studies indicated that this mutation may cause reduced enzymatic activity. After treatment with hydrocortisone and spironolactone, blood pressure was brought under good control, and menstruation returned to normal. We also conducted a retrospective review of previously reported cases in the literature (over 170 cases since 1991).ConclusionsEarly diagnosis of non-classical 11OHD is difficult because its symptoms are mild. The possibility of this disease should be considered in patients with early-onset hypertension, menstrual disorders, and hyperandrogenism to provide early treatment and prevent organ damage due to hypertension and hyperandrogenism. CYP11B1 mutations are known to be race-specific and are concentrated in exons 3 and 8, of which mutations in the former are mostly associated with non-classical 11OHD, whereas mutations in the latter are mostly found in classical 11OHD, characterized by severe loss of enzymatic activity.
“…The T318 M mutation is most common among Yemenis [ 2 , 27 , 28 ], and some new mutations such as c.53_54insT, G206 V, W260X, R448P, and H465L are often found in Saudi Arabs [ 29 – 31 ]. The R454C mutation has only been reported among the Chinese [ 8 , 10 , 32 ]. Fig.…”
Background11β-hydroxylase deficiency (11OHD) is extremely rare, and reports of non-classical 11OHD are even rarer. Non-classical 11OHD usually presents as premature adrenarche, hyperandrogenism, menstrual disorders, and hypertension. Because the symptoms of non-classical 11OHD are mild, delayed diagnosis or misdiagnosis as polycystic ovary syndrome or primary hypertension is common.Case presentationThis paper introduces a case of a young female patient presenting hypertension and menstrual disorders. Laboratory examination revealed increased androgen levels, mild adrenal hyperplasia, mild left ventricular hypertrophy, and mild sclerosis of the lower limb arteries. 11OHD was confirmed by genetic testing, and the patient was found to carry compound heterozygous mutations in CYP11B1 (c.583 T > C and c.1358G > A). The mutation Y195H is located in exon 3 and has not been reported previously. In silico studies indicated that this mutation may cause reduced enzymatic activity. After treatment with hydrocortisone and spironolactone, blood pressure was brought under good control, and menstruation returned to normal. We also conducted a retrospective review of previously reported cases in the literature (over 170 cases since 1991).ConclusionsEarly diagnosis of non-classical 11OHD is difficult because its symptoms are mild. The possibility of this disease should be considered in patients with early-onset hypertension, menstrual disorders, and hyperandrogenism to provide early treatment and prevent organ damage due to hypertension and hyperandrogenism. CYP11B1 mutations are known to be race-specific and are concentrated in exons 3 and 8, of which mutations in the former are mostly associated with non-classical 11OHD, whereas mutations in the latter are mostly found in classical 11OHD, characterized by severe loss of enzymatic activity.
“…Đột biến A368D làm giảm 1,17% hoạt tính của 11-deoxycortisol , đột biến R43Q làm hoạt tính 11-hydroxylase giảm từ 30-50% (Barr et al, 2006), đột biến L22P giảm 1,6% hoạt tính enzyme… Ngoài ra, khi kết hợp phân tích chức năng enzyme bằng tạo đột biến điểm trực tiếp và cấu trúc không gian sẽ cho chúng ta có hiểu biết sâu về mối quan hệ giữa cấu trúc và chức năng của enzyme (Bảng 2). Các đột biến xuất hiện trên toàn bộ 9 exon nhưng thường gặp trên exon 6 và exon 8 (Chabraoui et al, 2010;Kharrat et al, 2010;Parajes et al, 2010;Ye et al, 2010;Wu et al, 2011;Ben Charfeddine et al, 2012;Carvajal et al, 2012;Melcescu et al, 2012;Nguyen et al, 2012;Xu et al, 2012;Abbaszadegan et al, 2013;Alvarez-Madrazo et al, 2013;Menabo et al, 2013;M. Zhang et al, 2013;Kamrath et al, 2014;Kaynar et al, 2014;Matsubara et al, 2014;Polat et al, 2014;Alqahtani et al, 2015;Menabo et al, 2015;Mooij et al, 2015;Nguyen et al, 2015).…”
Section: Tình Hình Nghiên Cứu Bệnh Thiếu Hụt 11β-hydroxylaseunclassified
“…Điều này chỉ ra các amino acid quan trọng cũng như các vùng amino acid mã hóa quan trọng của enzyme. Ngoài dạng đột biến thay thế amino acid cũng có các đột biến khác được phát hiện như đột biến không mang nghĩa và đột biến chuyển khung đọc amino acid, các đột biến này cũng làm mất hoặc giảm hoạt tính enzyme (Cerame et al, 1999;Curnow et al, 1993;Chabraoui et al, 2010;Parajes et al, 2010;Wu et al, 2011;Carvajal et al, 2012;Xu et al, 2012;Abbaszadegan et al, 2013;Alvarez-Madrazo et al, 2013;Menabo et al, 2013;M. Zhang et al, 2013;Matsubara et al, 2014;Chabre et al, 2000;Chabre et al, 2000).…”
Section: Tình Hình Nghiên Cứu Bệnh Thiếu Hụt 11β-hydroxylaseunclassified
Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders which is characterized by a deficiency of one of the enzymes involved in the synthesis of cortisol from cholesterol by the adrenal cortex. 90% CAH patients respond to 21-hydroxylase deficiency. Less causes include deficiencies of 11β-hydroxylase (11-OH), 17- hydroxylase (17-OH), 3β- hydroxysteroid dehydrogenase (3β- HSD), 20/22 Desmolase etc.. Because of the blocked enzymatic steps, cortisol precursors usually presents with signs of androgen excess which are secreted and cause in masculinization of female external genital, hyponatremia, hyperkalemia and hypovolemia in the classic form due to 21-hydroxylase deficiency. By the early 1950s, it was recognized that in some CAH patients with hypertension develops. This symptom responds to glucorticoid replacement. Most of these patients have an 11β-hydroxylase deficiency. CAH cases arise from 11β-hydroxylase impaired is the second most common form. Mutations in the CYP11B1 gene are the cause of 11β-hydroxylase deficiency. The incident of 11β-hydroxylase deficiency is about 5% to 8% of cases with CAH, in approximately 1/100,000 live birth. Mutations have been detected from different ethnic backgrounds with the highest incidence in group of Morrocan Jews. This article reviews function of enzyme 11β-hydroxylase in cortisol synthesis of andrenal cortex, structure of CYP11B1 gene, diagnosis and treatment of 11β-hydroxylase deficiency and summarised of researching in Wordwild and in Vietnam. Genetic characterization of CYP11B1 genotype has improved our understanding of the phenotype differences in patients. This could be serve as a the basis for genetic counseling and prenatal diagnosis in the future.
“…Moreover, the excess of postnatal androgen causes androgenisation and rapid somatic growth as well as accelerated bone maturation in both sexes. The accumulation of DOC, which binds to and activates the mineralocorticoid receptor, leads to hypertension in about two-thirds of all patients (3,10,11,12,13). Hormonal diagnosis of 11OHD is verified by elevated baseline concentrations of DOC and S in classical forms as well as increased response to cosyntropin stimulation in non-classic forms (14).…”
Background: Congenital adrenal hyperplasia (CAH) is one of the most common autosomal recessive inherited endocrine diseases. Steroid 11b-hydroxylase (P450c11) deficiency (11OHD) is the second most common form of CAH. Aim: The aim of the study was to study the functional consequences of three novel CYP11B1 gene mutations (p.His125Thrfs*8, p.Leu463_Leu464dup and p.Ser150Leu) detected in patients suffering from 11OHD and to correlate this data with the clinical phenotype. Methods: Functional analyses were done by using a HEK293 cell in vitro expression system comparing WT with mutant P450c11 activity. Mutant proteins were examined in silico to study their effect on the three-dimensional structure of the protein.Results: Two mutations (p.His125Thrfs*8 and p.Leu463_Leu464dup) detected in patients with classic 11OHD showed a complete loss of P450c11 activity. The mutation (p.Ser150Leu) detected in a patient with non-classic 11OHD showed partial functional impairment with 19% of WT activity. Conclusion: Functional mutation analysis enables the correlation of novel CYP11B1 mutations to the classic and non-classic 11OHD phenotype respectively. Mutations causing a non-classic phenotype show typically partial impairment due to reduced maximum reaction velocity comparable with non-classic mutations in 21-hydroxylase deficiency. The increasing number of mutations associated with non-classic 11OHD illustrate that this disease should be considered as diagnosis in patients with otherwise unexplained hyperandrogenism.
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