Eugenio Arteaga1, Felipe Valenzuela2, Carlos F Lagos3, Marcela Lagos4, Alejandra Martinez2, Rene Baudrand2,5, Cristian Carvajal2, Carlos E Fardella2,5. 1. Departamento de Endocrinología and Centro Traslacional en Endocrinología (CETREN), Facultad de Medicina, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, Piso 4, Santiago Centro, 8330077, Santiago, Chile. eugenioarteaga@gmail.com. 2. Departamento de Endocrinología and Centro Traslacional en Endocrinología (CETREN), Facultad de Medicina, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, Piso 4, Santiago Centro, 8330077, Santiago, Chile. 3. Facultad de Medicina y Ciencia, Universidad San Sebastián, Campus Los Leones, Lota 2465, Providencia, 7510157, Santiago, Chile. 4. Departamento de Laboratorios Clínicos, Facultad de Medicina, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4686, Piso 3, Macul, 7820436, Santiago, Chile. 5. Instituto Milenio en Inmunología e Inmunoterapia IMII, Portugal 49, Santiago Centro, 8330075, Santiago, Chile.
Abstract
PURPOSE: 21-hydroxylase deficiency (21-OHD) is a congenital adrenal disease with more than 200 mutations published to date. The aim of this report is to describe a severe novel mutation of the CYP21A2 gene. METHOD: We describe a case of a 39-year-old male diagnosed with a salt wasting congenital adrenal hyperplasia (SWCAH) due to 21-OHD. The genetic testing was done using a combination of three methods (PCR XL, SALSA-MLPA, and bidirectional sequencing) and finally an in silico analysis. RESULTS: The genetic testing demonstrated three severe mutations of the CYP21A2 gene (p.Gln318*; c.290-13C>G; and p.Trp86*), being the last one a novel mutation not previously reported. The in silico modeling of the p.Trp86* (c.258G>A) showed a truncated CYP21A2 protein that loses all the main structural features required for activity, such as the HEM binding domain and the hormone binding site. CONCLUSION: We present an adult man with an SWCAH due to 21-OHD who carried three severe mutations of the CYP21A2 gene, one of them, p.Trp86* (c.258G>A) has not been previously described.
PURPOSE:21-hydroxylase deficiency (21-OHD) is a congenital adrenal disease with more than 200 mutations published to date. The aim of this report is to describe a severe novel mutation of the CYP21A2 gene. METHOD: We describe a case of a 39-year-old male diagnosed with a saltwasting congenital adrenal hyperplasia (SWCAH) due to 21-OHD. The genetic testing was done using a combination of three methods (PCR XL, SALSA-MLPA, and bidirectional sequencing) and finally an in silico analysis. RESULTS: The genetic testing demonstrated three severe mutations of the CYP21A2 gene (p.Gln318*; c.290-13C>G; and p.Trp86*), being the last one a novel mutation not previously reported. The in silico modeling of the p.Trp86* (c.258G>A) showed a truncated CYP21A2 protein that loses all the main structural features required for activity, such as the HEM binding domain and the hormone binding site. CONCLUSION: We present an adult man with an SWCAH due to 21-OHD who carried three severe mutations of the CYP21A2 gene, one of them, p.Trp86* (c.258G>A) has not been previously described.
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