Κατεύθυνση Κλινική Παιδιατρική & Νοσηλευτική - Έρευνα
Library of the School of Health Sciences

2014-08-01

2014

Βαρβαρέσου Αθανασία

Τζουμάκα-Μπακούλα Χρύσα

Καθορισμός των μεταλλάξεων του γονιδίου cyp21 και συσχετισμός του γονότυπου με το φαινότυπο σε κύπριους ασθενείς με συγγενή υπερπλασία επινεφριδίων

Greek

Abstract
Introduction:Congenital adrenal hyperplasia (CAH) due to steroid 21-
hydroxylase ( 21OH) deficiency is one of the most common inborn endocrine
disorders and is inherited as an autosomal recessivedisease. Molecular
abnormalities of the CYP21 gene coding for the steroid 21OH lead to various
degrees of impaired cortisol and aldosterone synthesis, and to androgen
excess. There are three major phenotypes depending on severity of the
enzymatic defect: the classical salt-wasting form, classicalsimple virilizing
form, both revealed at birth, and nonclassical form (NC-CAH) with late-onset
symptoms and diagnosis in childhood or after
Aim:Τo establish the type and frequency ofCYP21 gene mutations in 32
patients with congenital adrenal hyperplasia (CAH)and to determine the
genotype/phenotype relationship.
Material and Method:We studied 32 21OHD patients(10 with the classical
form and 22 with the non classical form).Ananalysis of the 21-hydroxylase
(21-OH) gene was performed by MLPA technique and direct sequencing of
PCR products.Mutations were divided into four groups (null,A,B,C).
Results:The most frequent genetic defect was p.V281L (54.7%) and IVS2-
13A/C 1 G (21.9%). In the classic salt-wasting and simple virilizing forms was
the IVS2-13A/C 1 G (55%) and in the non-classical form, the p.V281L(79.5%).
All patients in the null group,A and B presented with the classical form(SW or
SV) as expected and all patients in group C presented withthe NC form. NC
patients with mutations in both alleles were divided into two groups (mild/mild
vs mild/severe). When comparing the phenotypes of these two groups
(mild/mild mutations) and (mild/severe), the clinical phenotype was not
affected by the presence of a severe mutation. No significant differences
between the two groups (mild/severe and mild/mild) were detected with
respect to age of diagnosis either.(p=0,940).Mean basal and post-ACTH
17OHP in this studyshowed no significant difference between the two groups
(p=0,101 and p=0,189 retrospectivelly).In contrast,in the NC form most
patients were diagnosed after 8 years of age, while in the classical form
clinical symptomswere established before the age of 8(p=0,006) as
expected.Conclusion :The previously described major mutationswere found in this
study as well.We observed a good correlation between genotype and
phenotype,although differencesmay appear and caused by genetics or still
undefined factors.

CAH, Mutation, Gene, 21-hydroxylase, Genotype

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0

Yes

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https://pergamos.lib.uoa.gr/uoa/dl/object/1312101