Progress in molecular-genetic studies on congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

Zhao, Liqiang; Han, Shuang; Tian, Haoming

doi:10.1007/s12519-008-0016-8

Cited by 25 publications

(21 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the cases of 11β-OHD, our clinical and laboratory data were similar to those found in previous reports [Zhao et al, 2008], and the clinical diagnoses were corroborated by biochemical and molecular testing. In these cases, conversion of 11β-deoxycortisol and deoxycorticosterone to cortisol and corticosterone, respectively, were used to confirm the diagnoses.…”

Section: Discussionsupporting

confidence: 88%

New Genetic Abnormalities in Non-21α-Hydroxylase-Deficiency Congenital Adrenal Hyperplasia

Martín¹,

Nájera²,

Garibay³

et al. 2013

Sex Dev

View full text Add to dashboard Cite

Congenital adrenal hyperplasia comprises a group of autosomal recessive disorders of sexual differentiation and development that occur due to deficiencies in steroidogenic enzymes within the adrenal gland. Using clinical, biochemical, and sequencing data, we describe non-21α-hydroxylase deficiencies in 6 individuals from 4 families originating from endogamic regions in Mexico. Three individuals had 11β- hydroxylase deficiencies caused by 2 hitherto unreported mutations (P442L substitution and an 11-bp insertion in exon 5 of CYP11B1), while 3 individuals had 17α-hydroxylase/17,20-lyase deficiencies. Sequence-tagged site analysis of 8 individuals from 1 endogamic region suggested that the mutations likely occurred as a result of a founder effect. Although non-21α-hydroxylase enzymatic defects are rare in most populations, characterization of new mutations is important in order to understand the demographic, clinical, biochemical, and molecular variations that exist, and for both active and preventative management in individuals and their communities.

show abstract

Section: Discussionsupporting

confidence: 88%

New Genetic Abnormalities in Non-21α-Hydroxylase-Deficiency Congenital Adrenal Hyperplasia

Martín¹,

Nájera²,

Garibay³

et al. 2013

Sex Dev

View full text Add to dashboard Cite

show abstract

“…Furthermore, even single amino acid replacements downstream of exon 2 (e.g. R448H, E371G and G446V) can cause an almost complete loss of function, resulting in severe steroid metabolism impairment [23,24]. Hence, the mutation changes the conformation and function of CYP11B1, so that its biological effects are disturbed, and the 11-hydroxylase activity is lost.…”

Section: Discussionmentioning

confidence: 99%

Identification and Functional Characterization of a Large Deletion of the <b><i>CYP11B1</i></b> Gene Causing an 11β-Hydroxylase Deficiency in a Chinese Pedigree

Qiao²,

Liu³

et al. 2012

Horm Res Paediatr

View full text Add to dashboard Cite

Background: Steroid 11β-hydroxylase deficiency (11OHD) is the second most common cause of congenital adrenal hyperplasia. Inherited in an autosomal recessive manner, 11OHD is caused by mutations in the CYP11B1 gene. Objective: To identify the mutation causing 11OHD in a Chinese pedigree and analyze the functional consequences and phenotype associated with this mutation. Methods: A Chinese family with 11OHD was screened for mutations in the CYP11B1 gene. Mini-gene experiment was performed to mimic the natural splicing and outcome of the genetic variation. Results: Complete DNA sequencing of the CYP11B1 gene revealed a novel 449-bp homozygous deletion (g.2697del449) in the patient and a heterozygous deletion in both of the patient’s parents and sister. This mutation was predicted to lead to the skipping of part of exon 3 and all of exon 4 and inserting of part of intron 4 in the CYP11B1 mRNA. It generated a truncated protein and resulted in the complete destruction of the heme-binding domain of the enzyme. Conclusions: The novel deletion drastically affects normal protein structure and abolishes normal enzyme activity, leading to a severe phenotype of congenital adrenal hyperplasia due to 11OHD.

show abstract

“…It catalyzes the synthesis of cortisol and is regulated by ACTH. 6 CYP11B2 is responsible for aldosterone synthesis. It encodes a protein with 18-hydroxylase and 18-oxydase activities and much lower activity of 11β-hydroxylase.…”

Section: Introductionmentioning

confidence: 99%

“…5 CYP11B1 mutations are responsible for 11β-hydroxylase deficiency 6 with over 90 reported disease-causing CYP11B1 mutations. 7,8 Recombination between these two homologous genes is common, resulting in a chimeric gene which usually encodes for a protein with aldosterone synthase activity regulated by ACTH, the CYP11B1 promoter.…”

Section: Introductionmentioning

confidence: 99%

Genetic screening of non-classic CAH females with hyperandrogenemia identifies a novel CYP11B1 gene mutation

Shammas

Byrou

Phelan

et al. 2016

View full text Add to dashboard Cite

OBJeCTIve: Congenital adrenal hyperplasia (CAh) is an endocrine autosomal recessive disorder with various symptoms of diverse severity. Mild hyperandrogenemia is the most common clinical feature in non-classic CAh patients and 95% of the cases are identified by mutations in the CYP21A2 gene. In the present study, the second most common cause for non-classic CAh (NC-CAH), 11β-hydroxylase deficiency due to mutations in the CYP11B1 gene, is investigated. DesIgN: screening of the CYP21A2 and CYP11B1 genes by direct sequencing was carried out for the detection of possible genetic defects in patients with suspected CAh. ResULTs: It was observed that CYP11B1 variants co-exist only in rare cases along with mutations in CYP21A2 in patients clinically diagnosed with CAh. A total of 23 NC-CAh female patients out of 75 were identified with only one mutation in the CYP21A2 gene. The novel CYP11B1 gene mutation, p.val484Asp, was identified in a patient with CAh in the heterozygous state. The structural characterization of the novel p.val484Asp was found to likely cause distortion of the surrounding beta sheet and indirect destabilization of the cavity that occurs on the opposite face of the structural elements, leading to partial impairment of the enzymatic activity. CONCLUsIONs: CYP21A2 gene mutations are the most frequent genetic defects in cases of NC-CAh even when these patients are in the heterozygous state. These mutations have a diverse phenotype giving rise to a variable extent of cortisol synthesis impairment; it is also clear that CYP11B1 mutants are a rare type of defects causing CAh.

show abstract

Progress in molecular-genetic studies on congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

Cited by 25 publications

References 36 publications

New Genetic Abnormalities in Non-21α-Hydroxylase-Deficiency Congenital Adrenal Hyperplasia

New Genetic Abnormalities in Non-21α-Hydroxylase-Deficiency Congenital Adrenal Hyperplasia

Identification and Functional Characterization of a Large Deletion of the <b><i>CYP11B1</i></b> Gene Causing an 11β-Hydroxylase Deficiency in a Chinese Pedigree

Genetic screening of non-classic CAH females with hyperandrogenemia identifies a novel CYP11B1 gene mutation

Contact Info

Product

Resources

About