Reply: TUBB4A novel mutation reinforces the genotype–phenotype correlation of hypomyelination with atrophy of the basal ganglia and cerebellum

Abstract

Sir, We thank Dr Carvalho and colleagues for their insightful letter (Carvalho et al. , 2014), which compliments our recent paper on hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) (Hamilton et al. , 2014). The authors present two H-ABC patients with a TUBB4A mutation. One mutation is novel, one has been reported before in three patients (Carvalho et al. , 2014; Hamilton et al. , 2014). Carvalho et al. stress that their patients presented with a more severe phenotype than observed in the group of now 30 patients with the common c.745G > A, p.Asp249Asn mutation, reinforcing our previous suggestion of a genotype–phenotype correlation. In our paper, we compared the phenotypes of H-ABC patients with the common TUBB4A mutation and H-ABC patients with other TUBB4A mutations, but refrained from correlations within the group of patients with other mutations (Hamilton et al. , 2014). The growing number of publications now allows further analysis of the genotype–phenotype relationship. The overview of all published cases by Carvalho et al. in Table 2 (Carvalho et al. , 2014) provided us with the opportunity to look at the MRI and clinical characteristics …