Added value of next generation gene panel analysis for patients with elevated methylmalonic acid and no clinical diagnosis following functional studies of vitamin B-12 metabolism

作者：Pupavac Mihaela; Tian Xia; Chu Jordan; Wang Guoli; Feng Yanming; Chen Stella; Fenter Remington; Zhang Victor W; Wang Jing; Watkins David; Wong Lee Jun; Rosenblatt David S^*

来源：Molecular Genetics and Metabolism, 2016, 117(3): 363-368.

DOI：10.1016/j.ymgme.2016.01.008

• Next generation sequencing gene panel
• Methylmalonic acid
• Cobalamin metabolism
• Vitamin B-12
• Diagnostic test
• Functional studies

Next generation sequencing (NGS) based gene panel testing is increasingly available as a molecular diagnostic approach for inborn errors of metabolism. Over the past 40 years patients have been referred to the Vitamin B-12 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 SUCLGI 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.

• 出版日期2016-3
• 单位McGill