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.