Ba. Boston et al., ACTIVATING MUTATION IN THE STIMULATORY GUANINE-NUCLEOTIDE-BINDING PROTEIN IN AN INFANT WITH CUSHINGS-SYNDROME AND NODULAR ADRENAL-HYPERPLASIA, The Journal of clinical endocrinology and metabolism, 79(3), 1994, pp. 890-893
Cushing's syndrome in infancy is uncommon. In this report, we describe
an infant with ACTH-independent Cushing's syndrome in which an activa
ting mutation in the stimulatory G-protein (G(s alpha)) was detected.
The patient presented at 3 months of age with Cushingoid features, poo
r linear growth, and elevated liver enzymes. Plasma ACTH and dexametha
sone suppression test results were consistent with ACTH-independent Cu
shing's syndrome, and a subsequent adrenalectomy revealed bilateral ad
renocorticonodular hyperplasia. Asymptomatic lesions consistent with f
ibrous dysplasia were later detected on bone scan. Genomic DNA was ext
racted from adrenal, liver, and blood and amplified by polymerase chai
n reaction with G(s alpha) exon 8 primers. Using allele-specific oligo
nucleotide hybridization, the DNA was probed for known G(s alpha)-acti
vating mutations. A point mutation coding for an arginine to cysteine
substitution at codon 201 of exon 8 was detected in genomic DNA from t
his infant's adrenal, liver, and leukocytes. The mutation was detected
in nodular adrenal tissue, but was essentially absent in normal adren
al tissue. Activating mutations in the G(s alpha) gene have previously
been described in GH-secreting tumors, thyroid adenomas, and the McCu
ne-Albright syndrome and are probably involved in the pathogenesis of
adrenocorticonodular hyperplasia in this infant with Cushing's syndrom
e.