Kliničke, biokemijske i molekularne karakteristike bolesnika s neklasičnom kongenitalnom adrenalnom hiperplazijom zbog manjka 21-hidroksilaze [Clinical, biochemical and molecular characteristics of the patients with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency]

Krnić, Nevena (2014) Kliničke, biokemijske i molekularne karakteristike bolesnika s neklasičnom kongenitalnom adrenalnom hiperplazijom zbog manjka 21-hidroksilaze [Clinical, biochemical and molecular characteristics of the patients with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

BACKGROUND: Nonclassical congenital adrenal hyperplasia (NCCAH) due to partial 21-hydroxylase deficiency is caused by mutations of the CYP21A2 gene located on chromosome 6p21.3. The aim of this study was to determine CYP21A2 gene mutations frequency among Croatian NCCAH patients, the correlation between genotype, phenotype and 17-hydroxyprogesterone (17-OHP) levels and to evaluate the need for prenatal diagnosis. ----- SUBJECTS AND METHODS: A cohort of 49 patients (38 unrelated) with NCCAH (31 female/18 male) and 64 relatives was studied. The subjects were evaluated for virilization signs, basal and ACTH-stimulated 17-OHP levels were measured and HLA typing and CYP21A2 gene molecular analysis were performed. ----- RESULTS: The commonest mutation in our study group is Exon 7 (83.87%) and 70.87% patients carry one «moderate/severe» mutation. Exon 7 mutation correlated with HLA-B14 (p<0.0001). Genotype did not correlate with phenotype and 17-OHP levels. The 17-OHP cutoff levels of best sensitivity and specificity were 8.8 nmol/l for baseline and 39.2 nmol/l for ACTH stimulated 17-OHP levels. ----- CONCLUSION: Phenotype and 17-OHP levels do not correlate with genotype. Thus molecular analysis of CYP21A2 gene should be done in all patients. Due to the risk of birthing a child with classical CAH, all carriers of one «moderate/severe» mutation should undergo genetic counselling and CYP21A2 gene mutations analysis in the patients' partners.

Abstract in Croatian

UVOD: Neklasični oblik kongenitalne adrenalne hiperplazije (NKKAH) zbog djelomičnog manjka enzima 21-hidroksilaze uzrokovan je mutacijama gena CYP21A2 na kromosomu 6p21.3. Cilj istraživanja je utvrditi učestalost mutacija gena CYP21A2 u bolesnika s NKKAH-om u Hrvatskoj, ispitati odnos genotipa, fenotipa i koncentracija 17-hidroksiprogesterona (17-OHP), te utvrditi potrebu provođenja prenatalne dijagnostike. ----- ISPITANICI I METODE: Ispitano je 49 bolesnika (38 nesrodnih) s NKKAH-om (31 ženskih/18 muških), te 64 člana uže obitelji. Procijenjeni su klinički znakovi hipersekrecije androgena, izmjerene koncentracije 17-OHP bazalno i nakon stimulacije s ACTH, tipizirani geni HLA i ispitane mutacije gena CYP21A2. ----- REZULTATI: Najčešća mutacija u našoj skupini ispitanika je mutacija u egzonu 7 (83,87% bolesnika), a 70,97% bolesnika nosi jednu «umjereno tešku/tešku» mutaciju. Mutacija u ezgonu 7 povezana je s HLA-B14 (p<0,0001). Nije utvrđena korelacija genotipa s kliničkom slikom i koncentracijama 17-OHP. Granične vrijednosti koncentracija 17-OHP s najboljom osjetljivošću i specifičnošću su 8,8 nmol/l za bazalnu i 39,2 nmol/l za koncentraciju 17-OHP nakon stimulacije s ACTH. ----- ZAKLJUČAK: Klinička slika i koncentracije 17-OHP ne pokazuju korelaciju s genotipom. Stoga je u svih bolesnika nužno ispitati mutacije gena CYP21A2. Zbog rizika za rađanje djeteta s klasičnim oblikom KAH-e, nosiocima «umjereno teške/teške» mutacije potrebno je pružiti genetsko savjetovanje i ispitati mutacije gena CYP21A2 kod partnera bolesnika.

Item Type: Thesis (PhD)
Mentors:
Mentor
Dumić, Miroslav
Departments: Izvan medicinskog fakulteta
Depositing User: Marijan Šember
University: Sveučilište u Zagrebu
Institution: Medicinski fakultet
Number of Pages: 128
Status: Unpublished
Creators:
CreatorsEmail
Krnić, NevenaUNSPECIFIED
Date: 2 October 2014
Date Deposited: 28 Nov 2014 11:56
Last Modified: 28 Nov 2014 11:56
Subjects: /
Related URLs:
    URI: http://medlib.mef.hr/id/eprint/2172

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