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Whole-Exome Sequencing in the Differential Diagnosis of Primary Adrenal Insufficiency in Children.

Chan, LF; Campbell, DC; Novoselova, TV; Clark, AJL; Metherell, LA (2015) Whole-Exome Sequencing in the Differential Diagnosis of Primary Adrenal Insufficiency in Children. Front Endocrinol (Lausanne), 6. p. 113. https://doi.org/10.3389/fendo.2015.00113
SGUL Authors: Clark, Adrian John L

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Abstract

Adrenal insufficiency is a rare, but potentially fatal medical condition. In children, the cause is most commonly congenital and in recent years a growing number of causative gene mutations have been identified resulting in a myriad of syndromes that share adrenal insufficiency as one of the main characteristics. The evolution of adrenal insufficiency is dependent on the variant and the particular gene affected, meaning that rapid and accurate diagnosis is imperative for effective treatment of the patient. Common practice is for candidate genes to be sequenced individually, which is a time-consuming process and complicated by overlapping clinical phenotypes. However, with the availability, and increasing cost effectiveness of whole-exome sequencing, there is the potential for this to become a powerful diagnostic tool. Here, we report the results of whole-exome sequencing of 43 patients referred to us with a diagnosis of familial glucocorticoid deficiency (FGD) who were mutation negative for MC2R, MRAP, and STAR the most commonly mutated genes in FGD. WES provided a rapid genetic diagnosis in 17/43 sequenced patients, for the remaining 60% the gene defect may be within intronic/regulatory regions not covered by WES or may be in gene(s) representing novel etiologies. The diagnosis of isolated or familial glucocorticoid deficiency was only confirmed in 3 of the 17 patients, other genetic diagnoses were adrenal hypo- and hyperplasia, Triple A, and autoimmune polyendocrinopathy syndrome type I, emphasizing both the difficulty of phenotypically distinguishing between disorders of PAI and the utility of WES as a tool to achieve this.

Item Type: Article
Additional Information: Copyright © 2015 Chan, Campbell, Novoselova, Clark and Metherell. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: FGD, adrenal insufficiency, genetics, whole-exome sequencing, adrenal insufficiency, whole-exome sequencing, FGD, genetics
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Front Endocrinol (Lausanne)
Language: eng
Dates:
DateEvent
5 August 2015Published
10 July 2015Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
G0802796Medical Research CouncilUNSPECIFIED
MR/K020455/1Medical Research CouncilUNSPECIFIED
PubMed ID: 26300845
Web of Science ID: WOS:000378482300001
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/108654
Publisher's version: https://doi.org/10.3389/fendo.2015.00113

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