Evaluation of Clinical Findings and Molecular Genetic Results of the Patients with CACNA1A Variants: Single Center Experience (P13-9.007)

Abstract

<h3>Objective:</h3> To evaluate clinical findings and molecular genetic results of the patients with <i>CACNA1A</i> variants. <h3>Background:</h3> <i>CACNA1A</i>-related disorders comprise clinically and genetically heterogeneous neurological disorders. <h3>Design/Methods:</h3> In our center, eleven cases of <i>CACNA1A</i> variants (pathogenic/likely pathogenic/variant of uncertain significance (VUS)) were identified retrospectively in whole/clinical exome sequencing. <h3>Results:</h3> Patient 1 has heterozygous <i>de novo</i> c.3790G&gt;A pathogenic variant with epilepsy, developmental delay, ataxia, intentional tremor, positive Romberg’s test, paroxysmal tonic upward gaze, and deep perception problems. His EEG was unremarkable until age 5, and the most recent one showed hypsarrhythmia. Patient 2 had heterozygous <i>de novo</i> c.4991G&gt;A pathogenic variant with global developmental delay, his MRI, and EEG were normal, his ataxia was nonprogressive and improved in time. Patient 3 has c.7378_7402del likely pathogenic variant, he had developmental regression, increased DTRs, and dystonia. Her MRI demonstrated cerebellar atrophy. Patient 4 has heterozygous c.6595C&gt;T VUS with epilepsy, a tremor in the face and upper extremities, and increased DTRs. Patient 5 has heterozygous c.2678G&gt;C VUS, was diagnosed with atypical autism, and his neurological examination was unremarkable. Patient 6 has heterozygous c.2870G&gt;C VUS with developmental delay, gait disorder, and corneal ulceration. Two cases have VUS variants with heterozygous c.6775C&gt;T and c.1261C&gt;T, and they were developmentally normal and had no neurological or psychiatric disorders. Three cases have heterozygous c.6712C&gt;T, c.7114C&gt;T, and c.5986A&gt;C VUS, and they have various neurological findings; however, their overall condition would be explained via other genes’ pathogenic variations. <h3>Conclusions:</h3> We report two <i>de novo</i> pathogenic, one likely pathogenic variant, and eight variants of uncertain significance. <i>CACNA1A</i> variations can lead to a broad spectrum of neurological disorders. However, the genotype-phenotype correlation is unclear and needs to be confirmed in functional and larger studies, especially in cases with a non-specified phenotype. <b>Disclosure:</b> Ms. Ovunc has nothing to disclose. Dr. Kalayci Yigin has nothing to disclose. Serhat Guler has nothing to disclose. Dr. Cinar has nothing to disclose. Dr. Agirbaslo has nothing to disclose. Prof. Seven has nothing to disclose.