Multiplex ligation-dependent probe amplification analysis of the NR0B1(DAX1) locus enables explanation of phenotypic differences in patients with X-linked congenital adrenal hypoplasia.

Abstract

BACKGROUND/AIM
X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency and hypogonadic hypogonadism. It is caused by deletions or point mutations of the NR0B1 gene, on Xp21. AHC can be associated with glycerol kinase deficiency, Duchenne muscular dystrophy and mental retardation (MR), as part of a contiguous gene deletion syndrome. A synthetic probe set for multiplex ligation-dependent probe amplification analysis was developed to confirm and characterize NR0B1 deletions in patients with AHC and to correlate their genotypes with their divergent phenotypes.
RESULTS
In 2 patients, isolated AHC was confirmed, while a patient at risk for metabolic crisis was revealed as the deletion extends to the GK gene. A deletion extending to IL1RAPL1 was confirmed in both patients showing MR. Thus, a good genotype-phenotype correlation was confirmed.
CONCLUSIONS
Multiplex ligation-dependent probe amplification analysis is a valuable tool to detect NR0B1 and contiguous gene deletions in patients with AHC. It is especially helpful for IL1RAPL1 deletion detection as no clinical markers for MR are available. Furthermore, multiplex ligation-dependent probe amplification has the advantage to identify female carriers that, depending on the deletion extension, have a high risk of giving birth to children with MR, AHC, glycerol kinase deficiency and Duchenne muscular dystrophy.

Links

Publisher Full Text

Authors

Barbaro M, Bens S, Haake A, Peter M, Brämswig J, Holterhus PM, Lopez-Siguero JP, Menken U, Mix M, Sippell WG, Wedell A, Riepe FG

Institution

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. Michela.barbaro@ki.se

Source

Hormone research in pædiatrics 77:2 2012 pg 100-7

MeSH

Adolescent
Adrenal Hyperplasia, Congenital
Adult
Child
DAX-1 Orphan Nuclear Receptor
Female
Gene Deletion
Genetic Association Studies
Genetic Diseases, X-Linked
Genetic Loci
Heterozygote Detection
Humans
Infant
Interleukin-1 Receptor Accessory Protein
Male
Mental Retardation, X-Linked
Mothers
Multiplex Polymerase Chain Reaction
Nucleic Acid Amplification Techniques
Oligonucleotide Array Sequence Analysis
Sweden

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22456342