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Data from: Neurologic phenotypes associated with COL4A1/2 mutations: expanding the spectrum of disease


Zagaglia, Sara et al. (2019), Data from: Neurologic phenotypes associated with COL4A1/2 mutations: expanding the spectrum of disease, Dryad, Dataset,


Objective: To characterize the neurological phenotypes associated with COL4A1/2 mutations and to seek genotype-phenotype correlation. Methods We analyzed clinical, EEG and neuroimaging data of 44 new, and 55 previously reported patients with COL4A1/COL4A2 mutations. Results Childhood-onset focal seizures, frequently complicated by status epilepticus and resistance to anti-epileptic drugs, was the most common phenotype. EEG typically showed focal epileptiform discharges in the context of other abnormalities, including generalized sharp waves or slowing. In 46.4% of new patients with focal seizures, porencephalic cysts on brain MRI co-localized with the area of the focal epileptiform discharges. In patients with porencephalic cysts, brain MRI frequently also showed extensive white matter abnormalities, consistent with the finding of diffuse cerebral disturbance on EEG. Notably, we also identified a subgroup of patients with epilepsy as their main clinical feature, in which brain MRI showed non-specific findings, in particular periventricular leukoencephalopathy and ventricular asymmetry. Analysis of fifteen pedigrees suggested a worsening of the severity of clinical phenotype in succeeding generations, particularly when maternally inherited. Mutations associated with epilepsy were spread across COL4A1 and a clear genotype-phenotype correlation did not emerge. Conclusions COL4A1/COL4A2 mutations typically cause a severe neurological condition and a broader spectrum of milder phenotypes, in which epilepsy is the predominant feature. Early identification of patients carrying COL4A1/COL4A2 mutations may have important clinical consequences, whilst for research efforts, omission from large-scale epilepsy sequencing studies of individuals with abnormalities on brain MRI may generate misleading estimates of the genetic contribution to the epilepsies overall.

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