ClinVar

In a 37-year-old man with complex cortical dysplasia with other brain malformations-7 (CDCBM7; 610031) manifest as polymicrogyria, Jaglin et al. (2009) identified a heterozygous 793T-C transition in the TUBB2B gene, resulting in a phe265-to-leu (F265L) substitution. He had microcephaly, severe mental retardation, and seizures, but no neuromotor impairment. Brain imaging showed asymmetric polymicrogyria predominantly in the left frontal, parietal, and temporal lobes, including the hippocampus. Other abnormal features were a dysmorphic caudate and striatum, severe cerebellar atrophy, partial posterior agenesis of the corpus callosum, and hypoplasia of the pons. In vitro functional expression assays showed that the F265L-mutant protein had markedly impaired ability to form alpha/beta-tubulin heterodimers with little evidence of incorporation into well-defined microtubules. Jaglin et al. (2009) noted that severe defect observed in vitro and the relatively mild phenotype of this patient, suggested that there is no simple correlation between in vitro and clinical phenotype.