SMAD4 and Leigh syndrome: After the collection of data for this study, additional DV have been detected in other genes including BMPR1A, FAM175A, MLH1, RAD51C, RAD51D, SMAD4, STK11, and TP53. Of note, although MLH1 represents about 50% of all LS cases [4], no DV in this gene were detected via the 27-gene panel during the study period, and a limited number have been detected after the conclusion of the study.