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Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency
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| Zeitschriftentitel: | Clinical Endocrinology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , |
| In: | Clinical Endocrinology, 83, 2015, 5, S. 629-635 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
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| Schlagwörter: |
| author_facet |
Mooij, Christiaan F. Parajes, Silvia Rose, Ian T. Taylor, Angela E. Bayraktaroglu, Taner Wass, John A.H. Connell, John M.C. Ray, David W. Arlt, Wiebke Krone, Nils Mooij, Christiaan F. Parajes, Silvia Rose, Ian T. Taylor, Angela E. Bayraktaroglu, Taner Wass, John A.H. Connell, John M.C. Ray, David W. Arlt, Wiebke Krone, Nils |
|---|---|
| author |
Mooij, Christiaan F. Parajes, Silvia Rose, Ian T. Taylor, Angela E. Bayraktaroglu, Taner Wass, John A.H. Connell, John M.C. Ray, David W. Arlt, Wiebke Krone, Nils |
| spellingShingle |
Mooij, Christiaan F. Parajes, Silvia Rose, Ian T. Taylor, Angela E. Bayraktaroglu, Taner Wass, John A.H. Connell, John M.C. Ray, David W. Arlt, Wiebke Krone, Nils Clinical Endocrinology Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency Endocrinology, Diabetes and Metabolism Endocrinology |
| author_sort |
mooij, christiaan f. |
| spelling |
Mooij, Christiaan F. Parajes, Silvia Rose, Ian T. Taylor, Angela E. Bayraktaroglu, Taner Wass, John A.H. Connell, John M.C. Ray, David W. Arlt, Wiebke Krone, Nils 0300-0664 1365-2265 Wiley Endocrinology, Diabetes and Metabolism Endocrinology http://dx.doi.org/10.1111/cen.12834 <jats:title>Summary</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Steroid 11β‐hydroxylase (<jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1) deficiency (11<jats:styled-content style="fixed-case">OHD</jats:styled-content>) is the second most common form of congenital adrenal hyperplasia. Nonclassic or mild 11<jats:styled-content style="fixed-case">OHD</jats:styled-content> appears to be a rare condition. Our study assessed the residual <jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1 function of detected mutations, adding to the spectrum of mild 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>, and illustrates the variability of the clinical presentation of 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Patients and methods</jats:title><jats:p>Five patients presented with mild to moderate 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>. Two women presented with mild hirsutism and in one case with secondary amenorrhoea. Two men presented with precocious pseudopuberty, gynaecomastia and elevated blood pressure. One 46,<jats:styled-content style="fixed-case">XX</jats:styled-content> female patient was diagnosed with virilization of the external genitalia 2 years after birth. Direct <jats:styled-content style="fixed-case">DNA</jats:styled-content> sequencing was carried out to perform <jats:italic><jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1</jats:italic> mutation analysis. The <jats:italic><jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1</jats:italic> mutations were functionally characterized using an <jats:italic>in vitro</jats:italic> expression system.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:italic><jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1</jats:italic>‐inactivating mutations were detected in all patients. Two novel missense mutations (p.P42L and p.A297V) and the previously characterized p.R143W mutation had residual <jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1 activities between 10% and 27%. A novel p.L382R and the previously uncharacterized p.G444D mutation both caused complete loss of <jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1 enzymatic activity.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Mutations causing partial impairment of 11β‐hydroxylase activity (residual activity of 10% or above) are associated with a less severe clinical presentation of 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>, which can be classified as a nonclassic form. Our data demonstrate that patients with nonclassic 11<jats:styled-content style="fixed-case">OHD</jats:styled-content> can present with androgen excess, precocious pseudopuberty and increased blood pressure. Timely diagnosis of nonclassic 11<jats:styled-content style="fixed-case">OHD</jats:styled-content> and consequently initiation of personalized treatment is essential to prevent co‐morbidities caused by androgen excess and hypertension.</jats:p></jats:sec> Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency Clinical Endocrinology |
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Wiley, 2015 |
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mooij2015characterizationofthemoleculargeneticpathologyinpatientswith11bhydroxylasedeficiency |
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2015 |
| publisher |
Wiley |
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ai |
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ai |
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Clinical Endocrinology |
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49 |
| title |
Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency |
| title_unstemmed |
Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency |
| title_full |
Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency |
| title_fullStr |
Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency |
| title_full_unstemmed |
Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency |
| title_short |
Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency |
| title_sort |
characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency |
| topic |
Endocrinology, Diabetes and Metabolism Endocrinology |
| url |
http://dx.doi.org/10.1111/cen.12834 |
| publishDate |
2015 |
| physical |
629-635 |
| description |
<jats:title>Summary</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Steroid 11β‐hydroxylase (<jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1) deficiency (11<jats:styled-content style="fixed-case">OHD</jats:styled-content>) is the second most common form of congenital adrenal hyperplasia. Nonclassic or mild 11<jats:styled-content style="fixed-case">OHD</jats:styled-content> appears to be a rare condition. Our study assessed the residual <jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1 function of detected mutations, adding to the spectrum of mild 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>, and illustrates the variability of the clinical presentation of 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Patients and methods</jats:title><jats:p>Five patients presented with mild to moderate 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>. Two women presented with mild hirsutism and in one case with secondary amenorrhoea. Two men presented with precocious pseudopuberty, gynaecomastia and elevated blood pressure. One 46,<jats:styled-content style="fixed-case">XX</jats:styled-content> female patient was diagnosed with virilization of the external genitalia 2 years after birth. Direct <jats:styled-content style="fixed-case">DNA</jats:styled-content> sequencing was carried out to perform <jats:italic><jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1</jats:italic> mutation analysis. The <jats:italic><jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1</jats:italic> mutations were functionally characterized using an <jats:italic>in vitro</jats:italic> expression system.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:italic><jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1</jats:italic>‐inactivating mutations were detected in all patients. Two novel missense mutations (p.P42L and p.A297V) and the previously characterized p.R143W mutation had residual <jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1 activities between 10% and 27%. A novel p.L382R and the previously uncharacterized p.G444D mutation both caused complete loss of <jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1 enzymatic activity.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Mutations causing partial impairment of 11β‐hydroxylase activity (residual activity of 10% or above) are associated with a less severe clinical presentation of 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>, which can be classified as a nonclassic form. Our data demonstrate that patients with nonclassic 11<jats:styled-content style="fixed-case">OHD</jats:styled-content> can present with androgen excess, precocious pseudopuberty and increased blood pressure. Timely diagnosis of nonclassic 11<jats:styled-content style="fixed-case">OHD</jats:styled-content> and consequently initiation of personalized treatment is essential to prevent co‐morbidities caused by androgen excess and hypertension.</jats:p></jats:sec> |
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| author | Mooij, Christiaan F., Parajes, Silvia, Rose, Ian T., Taylor, Angela E., Bayraktaroglu, Taner, Wass, John A.H., Connell, John M.C., Ray, David W., Arlt, Wiebke, Krone, Nils |
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| description | <jats:title>Summary</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Steroid 11β‐hydroxylase (<jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1) deficiency (11<jats:styled-content style="fixed-case">OHD</jats:styled-content>) is the second most common form of congenital adrenal hyperplasia. Nonclassic or mild 11<jats:styled-content style="fixed-case">OHD</jats:styled-content> appears to be a rare condition. Our study assessed the residual <jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1 function of detected mutations, adding to the spectrum of mild 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>, and illustrates the variability of the clinical presentation of 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Patients and methods</jats:title><jats:p>Five patients presented with mild to moderate 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>. Two women presented with mild hirsutism and in one case with secondary amenorrhoea. Two men presented with precocious pseudopuberty, gynaecomastia and elevated blood pressure. One 46,<jats:styled-content style="fixed-case">XX</jats:styled-content> female patient was diagnosed with virilization of the external genitalia 2 years after birth. Direct <jats:styled-content style="fixed-case">DNA</jats:styled-content> sequencing was carried out to perform <jats:italic><jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1</jats:italic> mutation analysis. The <jats:italic><jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1</jats:italic> mutations were functionally characterized using an <jats:italic>in vitro</jats:italic> expression system.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:italic><jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1</jats:italic>‐inactivating mutations were detected in all patients. Two novel missense mutations (p.P42L and p.A297V) and the previously characterized p.R143W mutation had residual <jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1 activities between 10% and 27%. A novel p.L382R and the previously uncharacterized p.G444D mutation both caused complete loss of <jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1 enzymatic activity.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Mutations causing partial impairment of 11β‐hydroxylase activity (residual activity of 10% or above) are associated with a less severe clinical presentation of 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>, which can be classified as a nonclassic form. Our data demonstrate that patients with nonclassic 11<jats:styled-content style="fixed-case">OHD</jats:styled-content> can present with androgen excess, precocious pseudopuberty and increased blood pressure. Timely diagnosis of nonclassic 11<jats:styled-content style="fixed-case">OHD</jats:styled-content> and consequently initiation of personalized treatment is essential to prevent co‐morbidities caused by androgen excess and hypertension.</jats:p></jats:sec> |
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| spelling | Mooij, Christiaan F. Parajes, Silvia Rose, Ian T. Taylor, Angela E. Bayraktaroglu, Taner Wass, John A.H. Connell, John M.C. Ray, David W. Arlt, Wiebke Krone, Nils 0300-0664 1365-2265 Wiley Endocrinology, Diabetes and Metabolism Endocrinology http://dx.doi.org/10.1111/cen.12834 <jats:title>Summary</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Steroid 11β‐hydroxylase (<jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1) deficiency (11<jats:styled-content style="fixed-case">OHD</jats:styled-content>) is the second most common form of congenital adrenal hyperplasia. Nonclassic or mild 11<jats:styled-content style="fixed-case">OHD</jats:styled-content> appears to be a rare condition. Our study assessed the residual <jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1 function of detected mutations, adding to the spectrum of mild 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>, and illustrates the variability of the clinical presentation of 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>.</jats:p></jats:sec><jats:sec><jats:title>Patients and methods</jats:title><jats:p>Five patients presented with mild to moderate 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>. Two women presented with mild hirsutism and in one case with secondary amenorrhoea. Two men presented with precocious pseudopuberty, gynaecomastia and elevated blood pressure. One 46,<jats:styled-content style="fixed-case">XX</jats:styled-content> female patient was diagnosed with virilization of the external genitalia 2 years after birth. Direct <jats:styled-content style="fixed-case">DNA</jats:styled-content> sequencing was carried out to perform <jats:italic><jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1</jats:italic> mutation analysis. The <jats:italic><jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1</jats:italic> mutations were functionally characterized using an <jats:italic>in vitro</jats:italic> expression system.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:italic><jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1</jats:italic>‐inactivating mutations were detected in all patients. Two novel missense mutations (p.P42L and p.A297V) and the previously characterized p.R143W mutation had residual <jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1 activities between 10% and 27%. A novel p.L382R and the previously uncharacterized p.G444D mutation both caused complete loss of <jats:styled-content style="fixed-case">CYP</jats:styled-content>11B1 enzymatic activity.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Mutations causing partial impairment of 11β‐hydroxylase activity (residual activity of 10% or above) are associated with a less severe clinical presentation of 11<jats:styled-content style="fixed-case">OHD</jats:styled-content>, which can be classified as a nonclassic form. Our data demonstrate that patients with nonclassic 11<jats:styled-content style="fixed-case">OHD</jats:styled-content> can present with androgen excess, precocious pseudopuberty and increased blood pressure. Timely diagnosis of nonclassic 11<jats:styled-content style="fixed-case">OHD</jats:styled-content> and consequently initiation of personalized treatment is essential to prevent co‐morbidities caused by androgen excess and hypertension.</jats:p></jats:sec> Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency Clinical Endocrinology |
| spellingShingle | Mooij, Christiaan F., Parajes, Silvia, Rose, Ian T., Taylor, Angela E., Bayraktaroglu, Taner, Wass, John A.H., Connell, John M.C., Ray, David W., Arlt, Wiebke, Krone, Nils, Clinical Endocrinology, Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency, Endocrinology, Diabetes and Metabolism, Endocrinology |
| title | Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency |
| title_full | Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency |
| title_fullStr | Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency |
| title_full_unstemmed | Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency |
| title_short | Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency |
| title_sort | characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency |
| title_unstemmed | Characterization of the molecular genetic pathology in patients with 11β‐hydroxylase deficiency |
| topic | Endocrinology, Diabetes and Metabolism, Endocrinology |
| url | http://dx.doi.org/10.1111/cen.12834 |