A Novel Mutation in the<i>CYP11B1</i>Gene Causes Steroid 11<i>β</i>-Hydroxylase Deficient Congenital Adrenal Hyperplasia with Reversible Cardiomyopathy

Alqahtani, Mohammad A.; Shati, Ayed A.; Zou, Minjing; Alsuheel, Ali M.; Alhayani, Abdullah A; Al‐Qahtani, Saleh M.; Gilban, Hessa M.; Meyer, Brain F; Shi, Yufei

doi:10.1155/2015/595164

Cited by 13 publications

(4 citation statements)

References 25 publications

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“…We found that 41 compound heterozygotes or homozygotes for select missense or nonsense mutations-namely P49L, R141Q, W260X, G267S, L299P, T318M, T318R, A331V, Q356X, A368D, R374Q, V441G, G444D, G446V, and R448H-present with moderate to severe classic CAH because of 11β-hydroxylase, confirming prior results (3,(14)(15)(16)(17)(22)(23)(24). These patients were mainly from Croatia, Tunisia, Africa, Turkey, and Saudi Arabia.…”

Section: Discussionsupporting

confidence: 88%

Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

Khattab

Haider

Kumar

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

112

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Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11β-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of CYP11B1 revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11β-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clinical, genetic, hormonal, and structural effects of CYP11B1 gene mutations in the largest international cohort of 108 patients with steroid 11β-hydroxylase deficiency CAH.steroid hormones | missense mutations | classic CAH | ambiguous genitalia C ongenital adrenal hyperplasia (CAH) is a Mendelian disorder transmitted as an autosomal recessive trait. The most prevalent form of CAH arises from steroid 21-hydroxylase enzyme deficiency, accounting for ∼90-95% of all cases (1, 2). In contrast, CAH caused by steroid 11β-hydroxylase deficiency is considerably rare, with a prevalence of 5-8% (3), from which we estimate an overall frequency of 1 in 100,000 live births.Two homologous enzymes, 11β-hydroxylase and aldosterone synthase, are encoded by the CYP11B1 and CYP11B2 genes, respectively. The two genes are 40-kb apart, each comprising nine exons and mapped to chromosome 8q21-22 (3, 4) (Fig. 1A). In contrast to CYP21A2 and its CYP21A1P pseudogene, CYP11B1 and CYP11B2 are both active and do not have a pseudogene. The two encoded homologs, however, have distinct functions in cortisol and aldosterone synthesis, respectively (3). In the zona fasciculata, 11β-hydroxylase converts 11-deoxycortisol and 11-deoxycorticosterone to cortisol and corticosterone, respectively, and is regulated by adrenocorticotropic hormone secreted by the pituitary. In contrast, in the zona glomerulosa aldosterone synthase converts corticosterone to aldosterone with the intermediate production of 18-hydroxycorticosterone. These latter conversions are controlled mainly by the renin angiotensin II system and serum potassium concentration (3).Deficiency of 11β-hydroxylase prevents the conversion of 11-deoxycortisol to cortisol and 11-deoxycorticosterone to corticosterone. This results in high levels of 11-deoxycortisol and 11-deoxycorticosterone, respectively, which are shunted into the androgen synthesis pathway, resulting in high levels of the androgenic steroid, androstenedione. Female newborns are thus profoundly virilized and exhibit significant masculinization of the ex...

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Section: Discussionsupporting

confidence: 88%

Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

Khattab

Haider

Kumar

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

112

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“…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). Điều này chỉ ra các amino acid quan trọng cũng như các vùng amino acid mã hóa quan trọng của enzyme.…”

Section: Tình Hình Nghiên Cứu Bệnh Thiếu Hụt 11β-hydroxylaseunclassified

“…Các đột biến trên gen CYP11B1 được tìm thấy rất đa dạng và rải rác trên toàn bộ gen (Hình 2). Các đột biến này được phát hiện đa dạng trên các bệnh nhân ẩn tinh hoàn hai bên (Nour,Pacaud 2015); bệnh nhân u nang thận và Ca ++ hoá thận (Aswani et al, 2015); viêm cơ tim (Alqahtani et al, 2015); u tuyến thượng thận (Kaynar et al, 2014)…Tuy nhiên mối liên hệ giữa kiểu gen và kiểu hình cũng chưa được sáng tỏ. Mặt khác, tỷ lệ các loại đột biến ở các chủng tộc là khác nhau.…”

Section: Tình Hình Nghiên Cứu Bệnh Thiếu Hụt 11β-hydroxylaseunclassified

11β-hydroxylase deficiency disorders

Phương

Hải

Hoàng

2018

Vietnam J. Biotechnol.

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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.

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“…For clinicians and researchers, a major importance of the SPL is to determine normal penile length and consequently identify babies with abnormal sizes viz micropenis and macropenis; as these are associated with different potentially endangering conditions such as congenital adrenal hyperplasia and congenital hypopituitarism (5,6) It is therefore pertinent that there should be no under-or over-stretching while measuring the penile length, so as to avoid creating skewed references and thus, the wrong diagnoses (7). Globally, reference values generated from different communities on SPL have shown ethnic and racial variations in penile sizes in the newborn (7)(8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Flaccid penile length and stretch factor in the newborn

Fetuga¹,

Ogunlesi²,

Adekoya³

et al. 2021

REJHS

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Objective: Little is known about the flaccid penile length in the newborn and the degree of stretch of the penis among investigators while measuring the stretched penile length. This study aimed to document the flaccid penile length and the stretch factor in the newborn.Methods: This cross-sectional study was carried out on 200 term male infants within the first 72 hours of life. The flaccid penile length and the stretched penile length were measured with a wooden spatula and the stretch factor was calculated.Results: The mean (±SD) flaccid and stretched penile length were 30.9 ± 3.8 mm and 38.9 ± 4.0 mm respectively. The mean stretch factor was 26.4 %. Both testes had the same mean volume of 1.6 ± 0.5 ml. There was a significant correlation between flaccid and stretched penile lengths (r = 0.775, p = 0.000). The flaccid penile length was a significant predictor of the stretched penile length.Conclusion: This study has been able to determine the stretch factor while measuring the flaccid and stretch penile lengths in Nigerian newborn infants. It is recommended that the flaccid penile length be measured along with the stretched penile length and determine the stretch factor in order to compare how much investigators stretch the penis during measurement. This will allow for detailed comparison of penile anthropometry across different ethnic groups and races. Keywords: flaccid penile length, newborn, stretch factor, stretched penile length.

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A Novel Mutation in theCYP11B1Gene Causes Steroid 11β-Hydroxylase Deficient Congenital Adrenal Hyperplasia with Reversible Cardiomyopathy

Cited by 13 publications

References 25 publications

Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

11β-hydroxylase deficiency disorders

Flaccid penile length and stretch factor in the newborn

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