Literature review and the combination clinical phenotype ofTMEM126B mutations
In order to study the overall clinical phenotypic spectrum caused byTMEM126B (NM_018480.7) mutations, all published literatures were reviewed (Alston et al., 2016; Sánchez-Caballero et al., 2016; Theunissen et al., 2017). Upset-plot (Lex et al., 2014) unraveled recurrent clinical phenotypes mainly including muscle symptoms (100%, 10/10), developmental delay (30%, 3/10), and visual problems (20%, 2/10) (Figure 6A). The newly identified individual (II-1) was diagnosed with LS with the characteristic MRI presentations, bilateral abnormal signal in cerebral peduncle and pons (Figure 6A). All point mutations and frameshift mutations reported before are included here for the genotype spectrum study (Figure 6B). Interestingly, except our report, none of the mutation affected exon 2. Overall genotype-phenotype correlation of TMEM126B was analyzed by reviewing all the published literature, the enzymatic activity of the complex I in all patients decreased, and the phenotypes were various mainly the muscle intolerance, development delay (Table 1). II-1 was the only individual presented neurological symptoms and diagnosed as Leigh syndrome.