Functional and Structural Consequences of Nine CYP21A2 Mutations Ranging from Very Mild to Severe Effects
المؤلفون المشاركون
Barbaro, Michela
de Lemos-Marini, Sofia Helena Valente
de Paula Michelatto, Débora
Karlsson, Leif
Lusa, Ana Letícia Gori
Silva, Camila D’Almeida Mgnani
Östberg, Linus Joakim
Persson, Bengt
Guerra-Júnior, Gil
de Mello, Maricilda Palandi
Lajic, Svetlana
المصدر
International Journal of Endocrinology
العدد
المجلد 2016، العدد 2016 (31 ديسمبر/كانون الأول 2016)، ص ص. 1-10، 10ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2016-09-19
دولة النشر
مصر
عدد الصفحات
10
التخصصات الرئيسية
الملخص EN
We present the functional and structural effects of seven novel (p.Leu12Met, p.Arg16Cys, p.Ser101Asn, p.Ser202Gly, p.Pro267Leu, p.Gln389_Ala391del, and p.Thr450Met) and two previously reported but not studied (p.Ser113Phe and p.Thr450Pro) CYP21A2 mutations.
Functional analyses were complemented with in silico prediction of mutation pathogenicity based on the recently crystallized human CYP21A2 structure.
Mutated proteins were transiently expressed in COS-1 cells and enzyme activities towards 17-hydroxyprogesterone and progesterone were determined.
Residual enzyme activities between 43% and 97% were obtained for p.Arg16Cys, p.Ser101Asn, p.Ser202Gly, p.Pro267Leu, and p.Thr450Met, similar to the activities of the well-known nonclassic mutations p.Pro453Ser and p.Pro482Ser, whereas the p.Leu12Met variant showed an activity of 100%.
Conversely, the novel p.Ser113Phe, p.Gln389_Ala391del, and p.Thr450Pro mutations drastically reduced the enzyme function below 4%.
The K m values for all novel variants were in the same order of magnitude as for the wild-type protein except for p.The450Met.
The maximum velocity was decreased for all mutants except for p.Leu12Met.
We conclude that p.Leu12Met is a normal variant; the mutations p.Arg16Cys, p.Ser101Asn, p.Ser202Gly, p.Pro267Leu, and p.Thr450Met could be associated with very mild nonclassic CAH, and the mutations p.Ser113Phe, p.Gln389_Ala391del, and p.Thr450Pro are associated with classic CAH.
The obtained residual activities indicated a good genotype-phenotype correlation.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
de Paula Michelatto, Débora& Karlsson, Leif& Lusa, Ana Letícia Gori& Silva, Camila D’Almeida Mgnani& Östberg, Linus Joakim& Persson, Bengt…[et al.]. 2016. Functional and Structural Consequences of Nine CYP21A2 Mutations Ranging from Very Mild to Severe Effects. International Journal of Endocrinology،Vol. 2016, no. 2016, pp.1-10.
https://search.emarefa.net/detail/BIM-1105868
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
de Paula Michelatto, Débora…[et al.]. Functional and Structural Consequences of Nine CYP21A2 Mutations Ranging from Very Mild to Severe Effects. International Journal of Endocrinology No. 2016 (2016), pp.1-10.
https://search.emarefa.net/detail/BIM-1105868
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
de Paula Michelatto, Débora& Karlsson, Leif& Lusa, Ana Letícia Gori& Silva, Camila D’Almeida Mgnani& Östberg, Linus Joakim& Persson, Bengt…[et al.]. Functional and Structural Consequences of Nine CYP21A2 Mutations Ranging from Very Mild to Severe Effects. International Journal of Endocrinology. 2016. Vol. 2016, no. 2016, pp.1-10.
https://search.emarefa.net/detail/BIM-1105868
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1105868
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر