Identification of point mutations in the 21-hydroxylase gene in patients affected with congenital adrenal hyperplasia

Dora Fonseca; Andrés Gutiérrez; Claudia Silva; Mauricio Coll; Gustavo Malo; Camilo Orjuela; Clara Arteaga; Alejandro Giraldo

Identification of point mutations in the 21-hydroxylase gene in patients affected with congenital adrenal hyperplasia

Título traducido de la contribución: Identificación de mutaciones puntuales en el gen de la 21-hidroxilasa en pacientes afectados de hiperplasia suprarrenal congénita

Dora Fonseca
, Andrés Gutiérrez
, Claudia Silva
, Mauricio Coll
, Gustavo Malo
, Camilo Orjuela
, Clara Arteaga
, Alejandro Giraldo

Producción científica: Contribución a revista › Artículo de Investigación › revisión exhaustiva

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INTRODUCCIÓN: La hiperplasia suprarrenal congénita (HSC) es un trastorno autosómico recesivo debido a una secreción deficiente de cortisol. Aproximadamente el 95% de los casos de HSC están causados por defectos en el gen de la 21-hidrodilasa2 (CYPA2). El espectro de manifestaciones clínicas incluye una forma de expresión grave y otra leve. Se determinó la frecuencia de las siguientes mutaciones puntuales: P30L, empalme IVS2-12A/C-G, Del 8pb, I172N, cluster Ex6, V281L, Q318X, R356W y P453S. MATERIAL Y MÉTODOS: Los 58 pacientes eran 48 con la forma grave de HSC y 10 con la forma leve. Las mutaciones puntuales en el gen de la hidroxilasa se aislaron mediante PCR alelo-específica y PCR-ACRS (sitio de restricción creado por amplificación), y se determinó su frecuencia. RESULTADOS: Se identificaron alelos alternativos en el 82,8% de las muestras. Las mutaciones más frecuentes fueron el empalme IVS2-12A/C-G (26,7%), Q318X (21,5%), V281L (12,1%) e I172N (12,1%). DISCUSIÓN: Las mutaciones más frecuentes fueron similares a las observadas en otros países, excepto Q318X. Aunque su frecuencia era mayor pero similar a la observada en los países latinoamericanos, contrastaba con la de otros continentes e indicaba la posible influencia de los antecedentes genéticos en su expresión. Varias de las mutaciones se asociaron a formas clínicas específicas relacionadas con la actividad enzimática. En las formas más leves de HSC se detectaron varios alelos. Éstos eran importantes porque estos pacientes pueden tener hijos con las formas virilizante y de pérdida de sal. El reconocimiento de las formas alélicas de la HSC permitirá un asesoramiento genético y un diagnóstico prenatal más específicos.

Título traducido de la contribución	Identificación de mutaciones puntuales en el gen de la 21-hidroxilasa en pacientes afectados de hiperplasia suprarrenal congénita
Idioma original	Inglés estadounidense
Páginas (desde-hasta)	220-230
Número de páginas	11
Publicación	Biomédica : revista del Instituto Nacional de Salud
Volumen	25
N.º	2
Estado	Publicada - ene. 1 2005

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

ODS 3: Salud y bienestar

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Genética (clínica)

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@article{3b87fa3cf1264fd49940d9d0de0615ac,

title = "Identification of point mutations in the 21-hydroxylase gene in patients affected with congenital adrenal hyperplasia",

abstract = "INTRODUCTION: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder due to impaired cortisol secretion. Approximately 95\% of CAH cases are caused by defects in the 21-hydrodylase2 (CYPA2) gene. The spectrum of clinical manifestations includes a severe and mild form of expression. The frequency of the following point mutations was determined: P30L, IVS2-12A/C-G splice, Del 8pb, I172N, cluster Ex6, V281L, Q318X, R356W and P453S. MATERIALS AND METHODS: The 58 patients consisted of 48 with the severe form of CAH and 10 with the mild form. Point mutations in the hydroxylase gene were isolated by allele-specific PCR and PCR-ACRS (amplification created restriction site), and their frequency was determined. RESULTS: Alternate alleles were identified in 82.8\% of the samples. The most frequent mutations were IVS2-12A/C-G splice (26.7\%), Q318X (21.5\%), V281L (12.1\%) and I172N (12.1\%). DISCUSSION: The most frequent mutations were similar to those observed in other countries, except for Q318X. Although its frequency was higher but similar to that observed in Latin American countries, it contrasted with those of other continents and indicated the possible influence of genetic background in its expression. Several of the mutations were associated with specific clinical forms related to the enzyme activity. In the milder forms of CAH, several alleles were detected. These were important because these patients can have children with the virilizing and salt wasting forms. Recognition of the allelic forms of CAH will permit more specific genetic counseling and prenatal diagnosis.",

author = "Dora Fonseca and Andr{\'e}s Guti{\'e}rrez and Claudia Silva and Mauricio Coll and Gustavo Malo and Camilo Orjuela and Clara Arteaga and Alejandro Giraldo",

year = "2005",

month = jan,

day = "1",

language = "English (US)",

volume = "25",

pages = "220--230",

journal = "Biom{\'e}dica : revista del Instituto Nacional de Salud",

issn = "0120-4157",

publisher = "Instituto Nacional de Salud",

number = "2",

}

Identification of point mutations in the 21-hydroxylase gene in patients affected with congenital adrenal hyperplasia. / Fonseca, Dora; Gutiérrez, Andrés; Silva, Claudia et al.
En: Biomédica : revista del Instituto Nacional de Salud, Vol. 25, N.º 2, 01.01.2005, p. 220-230.

Producción científica: Contribución a revista › Artículo de Investigación › revisión exhaustiva

TY - JOUR

T1 - Identification of point mutations in the 21-hydroxylase gene in patients affected with congenital adrenal hyperplasia

AU - Fonseca, Dora

AU - Gutiérrez, Andrés

AU - Silva, Claudia

AU - Coll, Mauricio

AU - Malo, Gustavo

AU - Orjuela, Camilo

AU - Arteaga, Clara

AU - Giraldo, Alejandro

PY - 2005/1/1

Y1 - 2005/1/1

N2 - INTRODUCTION: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder due to impaired cortisol secretion. Approximately 95% of CAH cases are caused by defects in the 21-hydrodylase2 (CYPA2) gene. The spectrum of clinical manifestations includes a severe and mild form of expression. The frequency of the following point mutations was determined: P30L, IVS2-12A/C-G splice, Del 8pb, I172N, cluster Ex6, V281L, Q318X, R356W and P453S. MATERIALS AND METHODS: The 58 patients consisted of 48 with the severe form of CAH and 10 with the mild form. Point mutations in the hydroxylase gene were isolated by allele-specific PCR and PCR-ACRS (amplification created restriction site), and their frequency was determined. RESULTS: Alternate alleles were identified in 82.8% of the samples. The most frequent mutations were IVS2-12A/C-G splice (26.7%), Q318X (21.5%), V281L (12.1%) and I172N (12.1%). DISCUSSION: The most frequent mutations were similar to those observed in other countries, except for Q318X. Although its frequency was higher but similar to that observed in Latin American countries, it contrasted with those of other continents and indicated the possible influence of genetic background in its expression. Several of the mutations were associated with specific clinical forms related to the enzyme activity. In the milder forms of CAH, several alleles were detected. These were important because these patients can have children with the virilizing and salt wasting forms. Recognition of the allelic forms of CAH will permit more specific genetic counseling and prenatal diagnosis.

AB - INTRODUCTION: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder due to impaired cortisol secretion. Approximately 95% of CAH cases are caused by defects in the 21-hydrodylase2 (CYPA2) gene. The spectrum of clinical manifestations includes a severe and mild form of expression. The frequency of the following point mutations was determined: P30L, IVS2-12A/C-G splice, Del 8pb, I172N, cluster Ex6, V281L, Q318X, R356W and P453S. MATERIALS AND METHODS: The 58 patients consisted of 48 with the severe form of CAH and 10 with the mild form. Point mutations in the hydroxylase gene were isolated by allele-specific PCR and PCR-ACRS (amplification created restriction site), and their frequency was determined. RESULTS: Alternate alleles were identified in 82.8% of the samples. The most frequent mutations were IVS2-12A/C-G splice (26.7%), Q318X (21.5%), V281L (12.1%) and I172N (12.1%). DISCUSSION: The most frequent mutations were similar to those observed in other countries, except for Q318X. Although its frequency was higher but similar to that observed in Latin American countries, it contrasted with those of other continents and indicated the possible influence of genetic background in its expression. Several of the mutations were associated with specific clinical forms related to the enzyme activity. In the milder forms of CAH, several alleles were detected. These were important because these patients can have children with the virilizing and salt wasting forms. Recognition of the allelic forms of CAH will permit more specific genetic counseling and prenatal diagnosis.

UR - https://pubmed.ncbi.nlm.nih.gov/16022377/

M3 - Research Article

SN - 0120-4157

VL - 25

SP - 220

EP - 230

JO - Biomédica : revista del Instituto Nacional de Salud

JF - Biomédica : revista del Instituto Nacional de Salud

IS - 2

ER -

Identification of point mutations in the 21-hydroxylase gene in patients affected with congenital adrenal hyperplasia

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ODS de las Naciones Unidas

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