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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Cohen, Pinhas / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Feihong / Mericq, Veronica / Roth, Christian / Toppari, Jorma

Editorial Board Member: Battelino, Tadej / Buyukgebiz, Atilla / Cassorla, Fernando / Chrousos, George P. / Cutfield, Wayne / Fideleff, Hugo L. / Hershkovitz, Eli / Hiort, Olaf / LaFranchi, Stephen H. / Lanes M. D., Roberto / Mohn, Angelika / Root, Allen W. / Rosenfeld, Ron G. / Werther, George / Zadik, Zvi

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IMPACT FACTOR 2016: 1.233

CiteScore 2016: 1.09

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2191-0251
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Volume 29, Issue 5 (May 2016)

Issues

Improved molecular diagnosis of patients with neonatal diabetes using a combined next-generation sequencing and MS-MLPA approach

Gorka Alkorta-Aranburu / Madina Sukhanova / David Carmody
  • Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, Department of Medicine, The University of Chicago, Chicago, IL, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Trevor Hoffman / Latrice Wysinger / Jennifer Keller-Ramey / Zejuan Li / Amy Knight Johnson / Frances Kobiernicki / Shaun Botes / Carrie Fitzpatrick / Soma Das / Daniela del Gaudio
Published Online: 2016-02-19 | DOI: https://doi.org/10.1515/jpem-2015-0341

Abstract

Background: We evaluated a methylation-specific multiplex-ligation-dependent probe amplification (MS-MLPA) assay for the molecular diagnosis of transient neonatal diabetes mellitus (TNDM) caused by 6q24 abnormalities and assessed the clinical utility of using this assay in combination with next generation sequencing (NGS) analysis for diagnosing patients with neonatal diabetes (NDM).

Methods: We performed MS-MLPA in 18 control samples and 42 retrospective NDM cases with normal bi-parental inheritance of chromosome 6. Next, we evaluated 22 prospective patients by combining NGS analysis of 11 NDM genes and the MS-MLPA assay.

Results: 6q24 aberrations were identified in all controls and in 19% of patients with normal bi-parental inheritance of chromosome 6. The MS-MLPA/NGS combined approach identified a genetic cause in ~64% of patients with NDM of unknown etiology.

Conclusions: MS-MLPA is a reliable method to identify all known 6q24 abnormalities and comprehensive testing of all causes reveals a causal mutation in ~64% of patients.

Keywords: imprinting; methylation-specific multiplex ligation dependent probe amplification; neonatal diabetes mellitus; next-generation sequencing

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About the article

Corresponding author: Daniela del Gaudio, PhD, University of Chicago, 5841 S. Maryland Ave. MC.0077, Chicago, IL 60637, USA, Phone: +(773) 834-6751, Fax: +(773) 834-0556, E-mail:


Received: 2015-08-24

Accepted: 2016-01-04

Published Online: 2016-02-19

Published in Print: 2016-05-01


Citation Information: Journal of Pediatric Endocrinology and Metabolism, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2015-0341.

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