TY - JOUR
T1 - Improved molecular diagnosis of patients with neonatal diabetes using a combined next-generation sequencing and MS-MLPA approach
AU - Alkorta-Aranburu, Gorka
AU - Sukhanova, Madina
AU - Carmody, David
AU - Hoffman, Trevor
AU - Wysinger, Latrice
AU - Keller-Ramey, Jennifer
AU - Li, Zejuan
AU - Johnson, Amy Knight
AU - Kobiernicki, Frances
AU - Botes, Shaun
AU - Fitzpatrick, Carrie
AU - Das, Soma
AU - Del Gaudio, Daniela
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - imprinting
KW - methylation-specific multiplex ligation dependent probe amplification
KW - neonatal diabetes mellitus
KW - next-generation sequencing
UR - http://www.scopus.com/inward/record.url?scp=84969570353&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84969570353&partnerID=8YFLogxK
U2 - 10.1515/jpem-2015-0341
DO - 10.1515/jpem-2015-0341
M3 - Article
C2 - 26894574
AN - SCOPUS:84969570353
SN - 0334-018X
VL - 29
SP - 523
EP - 531
JO - Journal of Pediatric Endocrinology and Metabolism
JF - Journal of Pediatric Endocrinology and Metabolism
IS - 5
ER -