Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
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We analyzed our two new cases of infantile-onset epilepsy with developmental delay with de novo variant in TUBB2A and review the related literatures. Our two probands were both girls with infantile-onset epilepsy and global developmental delay. Case 1 had a novel de novo heterozygous missense variant: c.728C>T [p.Pro243Leu] (NM_001069.2). Her brain magnetic resonance imaging (MRI) showed nonspecific white matter myelination delay and slightly enlarged anterior horn of lateral ventricle. Her epilepsy had been controlled by TPM monotherapy. Case 2 had a reported de novo variant c.743C>T [p.Ala248Val] (NM_001069.2). Her brain MRI showed bilateral microgyria and corpus callosum dysplasia. A total of seven TUBB2A mutations cases had been published previously in five papers, therefore, until now, there were nine patients with TUBB2A mutations. All patients had developmental delay, among them seven cases also with infantile-onset epilepsy, one case with abnormal EEG but without clinical seizures. There are six cases that have different degree of cortical dysplasia, one case with cerebellar vermis atrophy and brainstem sacsinopathy, the rest two cases have no obvious brain structural abnormalities. There was one case with variant c.1249G>A (p.D417N) that had atypical clinical presentation, including prominent progressive spastic ataxia, sensory motor axonal neuropathy, and bilateral optic macular dystrophy, but relatively mild intellectual disability, his MRI showed cerebellar atrophy, thinning of the corpus callosum and pons sacsinopathy, but no cortical malformation. The p.A248V mutation was the most common mutation occurred in three patients (3/9). The clinical phenotypes of these three patients were similar, all of them had global developmental delay with no language and corpus callosum dysplasia, two cases with epilepsy and the other one only have EEG epileptic discharges without clinical seizure, two cases with cortical dysplasia and the other one without obvious brain malformation. In brief, global developmental delay was the most common phenotype of TUBB2A mutation-related disease, most cases also had infantile-onset epilepsy and cortical dysplasia and corpus callosum dysplasia. The region between seventh and eighth alpha-helix of TUBB2A may be a "hot spot" mutation domain.
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PMID:De novo mutations of TUBB2A cause infantile-onset epilepsy and developmental delay. 3220 52