Figure 3. Genotype–phenotype correlations.

Genetic testing results were available for 35 individuals. Twenty-seven unique mutations were identified. For genotype–phenotype assessment, mutations were categorized as nonsense (n = 17), missense (n = 10), or splice site (n = 8). Of note, 1 recurrent missense mutation (R69C in the PH-GRAM domain) has been shown to alter splicing (Pierson et al.¹⁴). (A) Mutation type and location. Mutations in MTM1 were found throughout the gene, and there was no obvious clustering in sections of the MTM1 gene coding for the known functional domains. Protein domain locations were defined by Laporte et al.¹⁵ (B) Mutation type and location in relationship to respiratory requirement. Because nearly all individuals required ventilatory support, there was no clear correlation between ventilation and mutation type, although a higher proportion of individuals with missense mutations did not need invasive support (4 of 10 missense on noninvasive support vs 0 of 17 nonsense and 1 of 8 splice site). (C) Mutation location and motor function. Other than 1 individual with a nonsense mutation, only individuals with missense mutations achieved the ability to ambulate independently (3 of 10).