Activating mutation in the stimulatory guanine nucleotide-binding protein in an infant with Cushing's syndrome and nodular adrenal hyperplasia

Bruce Boston, Scott Mandel, Stephen Lafranchi, Michael Bliziotes

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Cushing's syndrome in infancy is uncommon. In this report, we describe an infant with ACTH-independent Cushing's syndrome in which an activating mutation in the stimulatory G-protein (G(s)α) was detected. The patient presented at 3 months of age with Cushingoid features, poor linear growth, and elevated liver enzymes. Plasma ACTH and dexamethasone suppression test results were consistent with ACTH-independent Cushing's syndrome, and a subsequent adrenalectomy revealed bilateral adrenocorticonodular hyperplasia. Asymptomatic lesions consistent with fibrous dysplasia were later detected on bone scan. Genomic DNA was extracted from adrenal, liver, and blood and amplified by polymerase chain reaction with G(s)α exon 8 primers. Using allele-specific oligonucleotide hybridization, the DNA was probed for known G(s)α-activating mutations. A point mutation coding for an arginine to cysteine substitution at codon 201 of exon 8 was detected in genomic DNA from this infant's adrenal, liver, and leukocytes. The mutation was detected in nodular adrenal tissue, but was essentially absent in normal adrenal tissue. Activating mutations in the G(s)α gene have previously been described in GH- secreting tumors, thyroid adenomas, and the McCune-Albright syndrome and are probably involved in the pathogenesis of adrenocorticonodular hyperplasia in this infant with Cushing's syndrome.

Original languageEnglish (US)
Pages (from-to)890-893
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume79
Issue number3
DOIs
StatePublished - Sep 1994

Fingerprint

Guanine Nucleotides
Cushing Syndrome
Liver
Adrenocorticotropic Hormone
Hyperplasia
Carrier Proteins
Mutation
Exons
DNA
Tissue
Polymerase chain reaction
Polyostotic Fibrous Dysplasia
GTP-Binding Proteins
Oligonucleotides
Dexamethasone
Cysteine
Arginine
Tumors
Adrenalectomy
Bone

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Activating mutation in the stimulatory guanine nucleotide-binding protein in an infant with Cushing's syndrome and nodular adrenal hyperplasia. / Boston, Bruce; Mandel, Scott; Lafranchi, Stephen; Bliziotes, Michael.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 79, No. 3, 09.1994, p. 890-893.

Research output: Contribution to journalArticle

@article{4cf257d5bf9b43ba8425df8e1e5d8847,
title = "Activating mutation in the stimulatory guanine nucleotide-binding protein in an infant with Cushing's syndrome and nodular adrenal hyperplasia",
abstract = "Cushing's syndrome in infancy is uncommon. In this report, we describe an infant with ACTH-independent Cushing's syndrome in which an activating mutation in the stimulatory G-protein (G(s)α) was detected. The patient presented at 3 months of age with Cushingoid features, poor linear growth, and elevated liver enzymes. Plasma ACTH and dexamethasone suppression test results were consistent with ACTH-independent Cushing's syndrome, and a subsequent adrenalectomy revealed bilateral adrenocorticonodular hyperplasia. Asymptomatic lesions consistent with fibrous dysplasia were later detected on bone scan. Genomic DNA was extracted from adrenal, liver, and blood and amplified by polymerase chain reaction with G(s)α exon 8 primers. Using allele-specific oligonucleotide hybridization, the DNA was probed for known G(s)α-activating mutations. A point mutation coding for an arginine to cysteine substitution at codon 201 of exon 8 was detected in genomic DNA from this infant's adrenal, liver, and leukocytes. The mutation was detected in nodular adrenal tissue, but was essentially absent in normal adrenal tissue. Activating mutations in the G(s)α gene have previously been described in GH- secreting tumors, thyroid adenomas, and the McCune-Albright syndrome and are probably involved in the pathogenesis of adrenocorticonodular hyperplasia in this infant with Cushing's syndrome.",
author = "Bruce Boston and Scott Mandel and Stephen Lafranchi and Michael Bliziotes",
year = "1994",
month = "9",
doi = "10.1210/jc.79.3.890",
language = "English (US)",
volume = "79",
pages = "890--893",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "3",

}

TY - JOUR

T1 - Activating mutation in the stimulatory guanine nucleotide-binding protein in an infant with Cushing's syndrome and nodular adrenal hyperplasia

AU - Boston, Bruce

AU - Mandel, Scott

AU - Lafranchi, Stephen

AU - Bliziotes, Michael

PY - 1994/9

Y1 - 1994/9

N2 - Cushing's syndrome in infancy is uncommon. In this report, we describe an infant with ACTH-independent Cushing's syndrome in which an activating mutation in the stimulatory G-protein (G(s)α) was detected. The patient presented at 3 months of age with Cushingoid features, poor linear growth, and elevated liver enzymes. Plasma ACTH and dexamethasone suppression test results were consistent with ACTH-independent Cushing's syndrome, and a subsequent adrenalectomy revealed bilateral adrenocorticonodular hyperplasia. Asymptomatic lesions consistent with fibrous dysplasia were later detected on bone scan. Genomic DNA was extracted from adrenal, liver, and blood and amplified by polymerase chain reaction with G(s)α exon 8 primers. Using allele-specific oligonucleotide hybridization, the DNA was probed for known G(s)α-activating mutations. A point mutation coding for an arginine to cysteine substitution at codon 201 of exon 8 was detected in genomic DNA from this infant's adrenal, liver, and leukocytes. The mutation was detected in nodular adrenal tissue, but was essentially absent in normal adrenal tissue. Activating mutations in the G(s)α gene have previously been described in GH- secreting tumors, thyroid adenomas, and the McCune-Albright syndrome and are probably involved in the pathogenesis of adrenocorticonodular hyperplasia in this infant with Cushing's syndrome.

AB - Cushing's syndrome in infancy is uncommon. In this report, we describe an infant with ACTH-independent Cushing's syndrome in which an activating mutation in the stimulatory G-protein (G(s)α) was detected. The patient presented at 3 months of age with Cushingoid features, poor linear growth, and elevated liver enzymes. Plasma ACTH and dexamethasone suppression test results were consistent with ACTH-independent Cushing's syndrome, and a subsequent adrenalectomy revealed bilateral adrenocorticonodular hyperplasia. Asymptomatic lesions consistent with fibrous dysplasia were later detected on bone scan. Genomic DNA was extracted from adrenal, liver, and blood and amplified by polymerase chain reaction with G(s)α exon 8 primers. Using allele-specific oligonucleotide hybridization, the DNA was probed for known G(s)α-activating mutations. A point mutation coding for an arginine to cysteine substitution at codon 201 of exon 8 was detected in genomic DNA from this infant's adrenal, liver, and leukocytes. The mutation was detected in nodular adrenal tissue, but was essentially absent in normal adrenal tissue. Activating mutations in the G(s)α gene have previously been described in GH- secreting tumors, thyroid adenomas, and the McCune-Albright syndrome and are probably involved in the pathogenesis of adrenocorticonodular hyperplasia in this infant with Cushing's syndrome.

UR - http://www.scopus.com/inward/record.url?scp=0027934280&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027934280&partnerID=8YFLogxK

U2 - 10.1210/jc.79.3.890

DO - 10.1210/jc.79.3.890

M3 - Article

C2 - 8077378

AN - SCOPUS:0027934280

VL - 79

SP - 890

EP - 893

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 3

ER -