RESUMEN
We analyzed the GNAS1 gene in five patients with pseudohypoparathyroidism type 1a (PHP1a) by performing polymerase chain reaction, followed by sequencing all 13 exons of the gene, single-stranded conformational polymorphism (SSCP) or heteroduplex analysis (HD). Three novel mutations were discovered: (1) a de novo 3 bp insertion of CTG in codon 47 of exon 1; (2) a missense mutation 1103T in exon 4; and (3) a de novo mutation of Arg280Gly in exon 10. Two other mutations, previously described in the literature, include: (1) a de novo 4 bp deletion (deltaGACT) involving codons 189 and 190 in exon 7, and (2) a deletion of a cytosine nucleotide at codon 115 in exon 5. We conclude that mutational analysis of the GNAS1 gene is a strong supportive tool for the diagnosis of PHP1a, and is a useful adjunct to the synthetic parathyroid hormone infusion test for PTH resistance.
Asunto(s)
Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Seudohipoparatiroidismo/genética , Adolescente , Asia Sudoriental , Australia , Secuencia de Bases , Niño , Preescolar , Análisis Mutacional de ADN , Exones/genética , Femenino , Humanos , Masculino , Datos de Secuencia Molecular , Mutación Missense/genética , Seudohipoparatiroidismo/diagnóstico , Seudohipoparatiroidismo/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
UNLABELLED: X-linked congenital adrenal hypoplasia (CAH) presents classically with adrenal insufficiency within the first 6 months of life, as the fetal adrenal cortex progressively involutes. However, there is increasing recognition of delayed presentation after infancy with the need for accurate molecular diagnosis to avoid an erroneous diagnosis of other more common causes of adrenal insufficiency in childhood. We report our genetic studies of a pedigree with two affected boys presenting with late onset X-linked CAH, diagnosed by the presence of a known W171X mutation of the DAX-1 gene, in whom the mother was an obligate heterozygote. Unlike other causes of adrenal insufficiency, the significance of this diagnosis lies in the important association of hypogonadotropic hypogonadism, and the provision of accurate genetic counselling. CONCLUSION: This study demonstrates that genetic analysis for X-linked congenital adrenal hypoplasia is essential to confirm the diagnosis in prepubertal patients presenting with adrenal insufficiency after infancy.