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.
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.
Authors: Jessica L Hwang; Soo-Young Park; Honggang Ye; May Sanyoura; Ashley N Pastore; David Carmody; Daniela Del Gaudio; Janna F Wilson; Craig L Hanis; Xiaoming Liu; Gil Atzmon; Benjamin Glaser; Louis H Philipson; Siri Atma W Greeley Journal: Pediatr Diabetes Date: 2017-11-29 Impact factor: 4.866
Authors: May Sanyoura; Lisa Letourneau; Amy E Knight Johnson; Daniela Del Gaudio; Siri Atma W Greeley; Louis H Philipson; Rochelle N Naylor Journal: Diabetes Res Clin Pract Date: 2019-05-04 Impact factor: 5.602
Authors: Marcela Brissova; Rachana Haliyur; Diane Saunders; Shristi Shrestha; Chunhua Dai; David M Blodgett; Rita Bottino; Martha Campbell-Thompson; Radhika Aramandla; Gregory Poffenberger; Jill Lindner; Fong Cheng Pan; Matthias G von Herrath; Dale L Greiner; Leonard D Shultz; May Sanyoura; Louis H Philipson; Mark Atkinson; David M Harlan; Shawn E Levy; Nripesh Prasad; Roland Stein; Alvin C Powers Journal: Cell Rep Date: 2018-03-06 Impact factor: 9.423
Authors: Rachana Haliyur; John T Walker; May Sanyoura; Conrad V Reihsmann; Shristi Shrestha; Radhika Aramandla; Greg Poffenberger; Andrea H Ramirez; Sambra D Redick; Jenny Aurielle B Babon; Nripesh Prasad; Robert A Hegele; Sally C Kent; David M Harlan; Rita Bottino; Louis H Philipson; Marcela Brissova; Alvin C Powers Journal: J Endocr Soc Date: 2021-10-29