Diagnosis of X-linked Adrenal Hypoplasia Congenita by Mutation Analysis of the DAX1 Gene

Weiwen Guo, Antonio Baldini, Elizabeth A. Lindsay, Edward R B Mccabe, Charles G. Stone, Stacy A. Morgan, Stella I. Madu, Kenneth C. Copeland, Jestina S. Mason, Leslie G. Biesecker, Mary N B Horlick, Anjana L. Pettigrew, Elena Zanaria

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

To develop a rapid diagnostic approach to individuals with the X-linked cytomegalic form of adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) due to mutations in DAX1a new member of the nuclear hormone receptor gene superfamily. Molecular genetic diagnostic investigations of individuals with AHC and their relatives included polymerase chain reaction amplification of DAX1for identification of intragenic mutations and fluorescence in situ hybridization with a cosmid containing the DAX1gene for evaluation of larger deletions. Families that had males affected with AHC were evaluated for mutations involving the DAX1gene. DAX1mutations were identified in four families that had males affected with AHC. Two apparently independent pedigrees had an identical frame-shift mutation due to a single base pair deletion, and a third had a larger deletion involving the entire DAX1locus. The fourth family was evaluated by fluorescence in situ hybridization for prenatal diagnosis, and both the DAX1locus and the contiguous glycerol kinase region were deleted. Molecular genetic and molecular cytogenetic techniques represent rapid and complementary approaches to the diagnosis of mutations in the DAX1gene responsible for AHC and the associated HH. Specific diagnosis of the cause of adrenal insufficiency in these boys permits anticipatory management of the HH and prenatal counseling for parents of the affected child and other members of their families.

Original languageEnglish
Pages (from-to)324-330
Number of pages7
JournalJournal of the American Medical Association
Volume274
Issue number4
DOIs
Publication statusPublished - Jul 26 1995

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Hypogonadism
Mutation
Genes
Fluorescence In Situ Hybridization
Molecular Biology
Glycerol Kinase
Adrenal Insufficiency
Cosmids
Frameshift Mutation
Molecular Pathology
Cytogenetic Analysis
Pedigree
Cytoplasmic and Nuclear Receptors
Prenatal Diagnosis
Base Pairing
Counseling
Parents
X-linked adrenal hypoplasia congenita
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Guo, W., Baldini, A., Lindsay, E. A., Mccabe, E. R. B., Stone, C. G., Morgan, S. A., ... Zanaria, E. (1995). Diagnosis of X-linked Adrenal Hypoplasia Congenita by Mutation Analysis of the DAX1 Gene. Journal of the American Medical Association, 274(4), 324-330. https://doi.org/10.1001/jama.1995.03530040052040

Diagnosis of X-linked Adrenal Hypoplasia Congenita by Mutation Analysis of the DAX1 Gene. / Guo, Weiwen; Baldini, Antonio; Lindsay, Elizabeth A.; Mccabe, Edward R B; Stone, Charles G.; Morgan, Stacy A.; Madu, Stella I.; Copeland, Kenneth C.; Mason, Jestina S.; Biesecker, Leslie G.; Horlick, Mary N B; Pettigrew, Anjana L.; Zanaria, Elena.

In: Journal of the American Medical Association, Vol. 274, No. 4, 26.07.1995, p. 324-330.

Research output: Contribution to journalArticle

Guo, W, Baldini, A, Lindsay, EA, Mccabe, ERB, Stone, CG, Morgan, SA, Madu, SI, Copeland, KC, Mason, JS, Biesecker, LG, Horlick, MNB, Pettigrew, AL & Zanaria, E 1995, 'Diagnosis of X-linked Adrenal Hypoplasia Congenita by Mutation Analysis of the DAX1 Gene', Journal of the American Medical Association, vol. 274, no. 4, pp. 324-330. https://doi.org/10.1001/jama.1995.03530040052040
Guo, Weiwen ; Baldini, Antonio ; Lindsay, Elizabeth A. ; Mccabe, Edward R B ; Stone, Charles G. ; Morgan, Stacy A. ; Madu, Stella I. ; Copeland, Kenneth C. ; Mason, Jestina S. ; Biesecker, Leslie G. ; Horlick, Mary N B ; Pettigrew, Anjana L. ; Zanaria, Elena. / Diagnosis of X-linked Adrenal Hypoplasia Congenita by Mutation Analysis of the DAX1 Gene. In: Journal of the American Medical Association. 1995 ; Vol. 274, No. 4. pp. 324-330.
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