domingo, 7 de febrero de 2016

Added value of next generation gene panel analysis for patients with elevated methylmalonic acid and no clinical diagnosis following functional stu... - PubMed - NCBI

2016 Jan 23. pii: S1096-7192(16)30007-5. doi: 10.1016/j.ymgme.2016.01.008. [Epub ahead of print]

Added value of next generation gene panel analysis for patients with elevated methylmalonic acid and no clinical diagnosis following functional studies of vitamin B12 metabolism.

Pupavac M1, Tian X2, Chu J1, Wang G2, Feng Y2, Chen S2, Fenter R2, Zhang VW3, Wang J3, Watkins D1, Wong LJ3, Rosenblatt DS4.

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Abstract

Next generation sequencing (NGS) based gene panel testing is increasingly available as a molecular diagnostic approach for inborn errors of metabolism. Over the past 40years patients have been referred to the Vitamin B12 Clinical Research Laboratory at McGill University for diagnosis of inborn errors of cobalamin metabolism by functional studies in cultured fibroblasts. DNA samples from patients in which no diagnosis was made by these studies were tested by a NGS gene panel to determine whether any molecular diagnoses could be made. 131 DNA samples from patients with elevated methylmalonic acid and no diagnosis following functional studies of cobalamin metabolism were analyzed using the 24 gene extended cobalamin metabolism NGS based panel developed by Baylor Miraca Genetics Laboratories. Gene panel testing identified two or more variants in a single gene in 16/131 patients. Eight patients had pathogenic findings, one had a finding of uncertain significance, and seven had benign findings. Of the patients with pathogenic findings, five had mutations in ACSF3, two in SUCLG1 and one in TCN2. Thus, the NGS gene panel allowed for the presumptive diagnosis of 8 additional patients for which a diagnosis was not made by the functional assays.