A Case of Salt-Wasting Congenital Adrenal Hyperplasia with Triple Homozygous Mutation: Review of Literature

Maria Laura Iezzi; Gaia Varriale; Luca Zagaroli; Stefania Lasorella; Marco Greco; Giulia Iapadre; Alberto Verrotti

doi:10.1055/s-0040-1705110

Journal of Pediatric Genetics, Inhaltsverzeichnis

J Pediatr Genet 2021; 10(01): 057-062
DOI: 10.1055/s-0040-1705110

Case Report

A Case of Salt-Wasting Congenital Adrenal Hyperplasia with Triple Homozygous Mutation: Review of Literature

Maria Laura Iezzi

¹Department of Pediatrics, Ospedale Civile San Salvatore, L'Aquila, Italy

,

Gaia Varriale

²Department of Pediatrics, University of L'Aquila, L'Aquila, Italy

,

Luca Zagaroli

²Department of Pediatrics, University of L'Aquila, L'Aquila, Italy

,

Stefania Lasorella

²Department of Pediatrics, University of L'Aquila, L'Aquila, Italy

,

Marco Greco

²Department of Pediatrics, University of L'Aquila, L'Aquila, Italy

,

Giulia Iapadre

²Department of Pediatrics, University of L'Aquila, L'Aquila, Italy

,

Alberto Verrotti

²Department of Pediatrics, University of L'Aquila, L'Aquila, Italy

› Institutsangaben

Abstract

Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency represents a group of autosomal recessive disorders characterized by impaired cortisol production due to altered upstream steroid conversions, subclassified as classic and nonclassic forms. The genotype–phenotype correlation is possible in the most frequent case but not in all. Despite in literature many mutations are known, there is the possibility of finding a new genetic pattern in patients with CAH.

Keywords

salt-wasting CAH - homozygous - CYP21A2 mutation - Q318X - R356W - R369Q

Volltext

Referenzen

References
1 Merke DP, Bornstein SR. Congenital adrenal hyperplasia. Lancet 2005; 365 (9477): 2125-2136
2 Pang S, Clark A, Neto EC. et al. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: newborn screening and its relationship to the diagnosis and treatment of the disorder. Screening 1993; 2 (2–3): 105-139
3 Grumbach MM, Shaw EB. Further studies on the treatment of congenital adrenal hyperplasia with cortisone: IV. Effect of cortisone and compound B in infants with disturbed electrolyte metabolism, by John F. Crigler Jr, MD, Samuel H. Silverman, MD, and Lawson Wilkins, MD, Pediatrics, 1952;10:397-413. Pediatrics 1998; 102 (1 Pt 2): 215-221
4 Therrell BL. Newborn screening for congenital adrenal hyperplasia. Endocrinol Metab Clin North Am 2001; 30 (01) 15-30
5 Oelkers WK. Effects of estrogens and progestogens on the renin-aldosterone system and blood pressure. Steroids 1996; 61 (04) 166-171
6 Balsamo A, Baldazzi L, Menabò S, Cicognani A. Impact of molecular genetics on congenital adrenal hyperplasia management. Sex Dev 2010; 4 (4-5): 233-248
7 Speiser PW, Azziz R, Baskin LS. et al; Endocrine Society. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010; 95 (09) 4133-4160
8 Barbaro M, Lajic S, Baldazzi L. et al. Functional analysis of two recurrent amino acid substitutions in the CYP21 gene from Italian patients with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2004; 89 (05) 2402-2407
9 Torres N, Mello MP, Germano CMR, Elias LLK, Moreira AC, Castro M. Phenotype and genotype correlation of the microconversion from the CYP21A1P to the CYP21A2 gene in congenital adrenal hyperplasia. Braz J Med Biol Res 2003; 36 (10) 1311-1318
10 Concolino P, Mello E, Toscano V, Ameglio F, Zuppi C, Capoluongo E. Multiplex ligation-dependent probe amplification (MLPA) assay for the detection of CYP21A2 gene deletions/duplications in congenital adrenal hyperplasia: first technical report. Clin Chim Acta 2009; 402 (1-2): 164-170
11 Bruque CD, Delea M, Fernández CS. et al. Structure-based activity prediction of CYP21A2 stability variants: a survey of available gene variations. Sci Rep 2016; 6: 39082
12 Haider S, Islam B, D'Atri V. et al. Structure-phenotype correlations of human CYP21A2 mutations in congenital adrenal hyperplasia. Proc Natl Acad Sci U S A 2013; 110 (07) 2605-2610
13 Lee HH. CYP21 mutations and congenital adrenal hyperplasia. Clin Genet 2001; 59 (05) 293-301
14 Janner M, Pandey AV, Mullis PE, Flück CE. Clinical and biochemical description of a novel CYP21A2 gene mutation 962_963insA using a new 3D model for the P450c21 protein. Eur J Endocrinol 2006; 155 (01) 143-151
15 White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev 2000; 21 (03) 245-291
16 Hsu LC, Hsu NC, Guzova JA, Guzov VM, Chang SF, Chung BC. The common I172N mutation causes conformational change of cytochrome P450c21 revealed by systematic mutation, kinetic, and structural studies. J Biol Chem 1996; 271 (06) 3306-3310
17 Balsamo A, Cacciari E, Baldazzi L. et al. CYP21 analysis and phenotype/genotype relationship in the screened population of the Italian Emilia-Romagna region. Clin Endocrinol (Oxf) 2000; 53 (01) 117-125
18 Delague V, Souraty N, Khallouf E. et al. Mutational analysis in Lebanese patients with congenital adrenal hyperplasia due to a deficit in 21-hydroxylase. Horm Res 2000; 53 (02) 77-82
19 Krone N, Braun A, Roscher AA, Knorr D, Schwarz HP. Predicting phenotype in steroid 21-hydroxylase deficiency? Comprehensive genotyping in 155 unrelated, well defined patients from southern Germany. J Clin Endocrinol Metab 2000; 85 (03) 1059-1065
20 Dracopoulou-Vabouli M, Maniati-Christidi M, Dacou-Voutetakis C. The spectrum of molecular defects of the CYP21 gene in the Hellenic population: variable concordance between genotype and phenotype in the different forms of congenital adrenal hyperplasia. J Clin Endocrinol Metab 2001; 86 (06) 2845-2848
21 Loke KY, Lee YS, Lee WW, Poh LK. Molecular analysis of CYP-21 mutations for congenital adrenal hyperplasia in Singapore. Horm Res 2001; 55 (04) 179-184
22 Pinto G, Tardy V, Trivin C. et al. Follow-up of 68 children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: relevance of genotype for management. J Clin Endocrinol Metab 2003; 88 (06) 2624-2633
23 Stikkelbroeck NM, Hoefsloot LH, de Wijs IJ, Otten BJ, Hermus AR, Sistermans EA. CYP21 gene mutation analysis in 198 patients with 21-hydroxylase deficiency in The Netherlands: six novel mutations and a specific cluster of four mutations. J Clin Endocrinol Metab 2003; 88 (08) 3852-3859
24 Kharrat M, Tardy V, M'Rad R. et al. Molecular genetic analysis of Tunisian patients with a classic form of 21-hydroxylase deficiency: identification of four novel mutations and high prevalence of Q318X mutation. J Clin Endocrinol Metab 2004; 89 (01) 368-374
25 Baradaran-Heravi A, Vakili R, Robins T. et al. Three novel CYP21A2 mutations and their protein modelling in patients with classical 21-hydroxylase deficiency from northeastern Iran. Clin Endocrinol (Oxf) 2007; 67 (03) 335-341
26 Wilson RC, Nimkarn S, Dumic M. et al. Ethnic-specific distribution of mutations in 716 patients with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Mol Genet Metab 2007; 90 (04) 414-421
27 Abid F, Tardy V, Gaouzi A, El Hessni A, Morel Y, Chabraoui L. CYP21A2 gene mutation analysis in Moroccan patients with classic form of 21-hydroxylase deficiency: high regional prevalence of p.Q318X mutation and identification of a novel p.L353R mutation. Clin Chem Lab Med 2008; 46 (12) 1707-1713
28 Sadeghi F, Yurur-Kutlay N, Berberoglu M. et al. Identification of frequency and distribution of the nine most frequent mutations among patients with 21-hydroxylase deficiency in Turkey. J Pediatr Endocrinol Metab 2008; 21 (08) 781-787
29 Tardy V, Menassa R, Sulmont V. et al. Phenotype-genotype correlations of 13 rare CYP21A2 mutations detected in 46 patients affected with 21-hydroxylase deficiency and in one carrier. J Clin Endocrinol Metab 2010; 95 (03) 1288-1300
30 Vrzalová Z, Hrubá Z, St'ahlová Hrabincová E. et al. Identification of CYP21A2 mutant alleles in Czech patients with 21-hydroxylase deficiency. Int J Mol Med 2010; 26 (04) 595-603
31 Finkielstain GP, Chen W, Mehta SP. et al. Comprehensive genetic analysis of 182 unrelated families with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 2011; 96 (01) E161-E172
32 Rabbani B, Mahdieh N, Ashtiani MT. et al. Mutation analysis of the CYP21A2 gene in the Iranian population. Genet Test Mol Biomarkers 2012; 16 (02) 82-90
33 Toraman B, Ökten A, Kalay E. et al. Investigation of CYP21A2 mutations in Turkish patients with 21-hydroxylase deficiency and a novel founder mutation. Gene 2013; 513 (01) 202-208
34 Mendes C, Vaz Matos I, Ribeiro L, Oliveira MJ, Cardoso H, Borges T. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: genotype-phenotype correlation. Acta Med Port 2015; 28 (01) 56-62
35 Milacic I, Barac M, Milenkovic T. et al. Molecular genetic study of congenital adrenal hyperplasia in Serbia: novel p.Leu129Pro and p.Ser165Pro CYP21A2 gene mutations. J Endocrinol Invest 2015; 38 (11) 1199-1210
36 Mohamed S, El-Kholy S, Al-Juryyan N, Al-Nemri AM, Abu-Amero KK. A CYP21A2 gene mutation in patients with congenital adrenal hyperplasia. Molecular genetics report from Saudi Arabia. Saudi Med J 2015; 36 (01) 113-116
37 Khajuria R, Walia R, Bhansali A, Prasad R. The spectrum of CYP21A2 mutations in congenital adrenal hyperplasia in an Indian cohort. Clin Chim Acta 2017; 464: 189-194
38 Liu SY, Lee CT, Tung YC, Chien YH, Hwu WL, Tsai WY. Clinical characteristics of Taiwanese children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency detected by neonatal screening. J Formos Med Assoc 2018; 117 (02) 126-131
39 Zhang B, Lu L, Lu Z. Molecular diagnosis of Chinese patients with 21-hydroxylase deficiency and analysis of genotype-phenotype correlations. J Int Med Res 2017; 45 (02) 481-492