At present, only one gene (GPR56) is known to cause polymicrogyria, which leads to a distinctive phenotype termed bilateral frontoparietal polymicrogyria (BFPP).
We identified homozygous GPR56 mutations in 14 patients from eight consanguineous families with typical bilateral bifrontoparietal polymicrogyria and in one foetal case, out of 30 patients with bifrontoparietal polymicrogyria referred for molecular screening.
Functional studies of the GPR56 gene product will yield insights not only into the causes of polymicrogyria but also into the mechanisms of normal cortical development and the regional patterning of the cerebral cortex.
Human cerebral cortical polymicrogyria is a heterogeneous disorder, with only one known gene (GPR56) associated with an apparently distinctive phenotype, termed bilateral frontoparietal polymicrogyria (BFPP).
Foetal TUBA1A tubulinopathies most often consist in microlissencephaly or classical lissencephaly with corpus callosum agenesis, but polymicrogyria may also occur.
We describe the clinical and neuroradiological features of a 3 years old girl carrying a novel missense TUBA1A mutation associated with asymmetrical polymicrogyria and provide structural data about the mutation.
In this study, we sequenced the TUBB2B and TUBA1A coding regions in 47 patients with a diagnosis of polymicrogyria and five with an atypical lissencephaly on neuroimaging.
These findings broaden the phenotypic spectrum associated with TUBA1A mutations to PMG and further emphasize that additional brain abnormalities, that is, dysmorphic basal ganglia, hypoplastic pons and cerebellar dysplasia are key features for the diagnosis of TUBA1A-related PMG.
Recently, de novo missense mutations in the tubulin α-1A (TUBA1A) gene were identified as causing a distinctive radiologic phenotype comprising of posteriorly predominant lissencephaly with dysgenetic corpus callosum, cerebellar and brainstem hypoplasia, and more recently, polymicrogyria.
Band like calcification with simplified gyration and polymicrogyria (BLC-PMG) is a distinct neuroradiological phenotype initially reported as a pseudo-TORCH syndrome and known to result from biallelic mutations in the Occludin(OCLN) gene.
This report underlines that the association of polymicrogyria with thin or absent corpus callosum, dysmorphic basal ganglia, brainstem and vermis hypoplasia is highly likely to result from mutations in TUBB2B and provides further insight in how mutations in TUBB2B affect protein function.
Furthermore, the lack of polymicrogyria associated with the rearrangement of OCLN in our patients extends the range of cranial defects that can be observed due to OCLN mutations.
We have identified a novel inherited heterozygous missense mutation in TUBB2B that results in an E421K amino acid substitution in a family who segregates congenital fibrosis of the extraocular muscles (CFEOM) with polymicrogyria.