Whole Exome Sequencing for the Diagnosis of Rare Genetic Neurodevelopmental Disorders Associated with Cerebellar Atrophy

Abstract Neurodegenerative disorders (NDs) are rare multifactorial disorders characterized by dysfunction and degeneration of synapses, neurons, and glial cells which are essential for movement, coordination, muscle strength, sensation and cognition. It may also be associated with neuroinflammation and oxidative stress. Several genes have been identified underlying the different forms. Herein, we describe seven patients from 6 Egyptian families. The core clinical features of our patients included dysmorphic features, neurodevelopmental delay or regression, gait abnormalities, skeletal deformities, visual impairment, and seizures. Previously unreported clinical phenotypic findings were recorded. Whole-exome sequencing (WES) was performed followed by in silico analysis of the detected genetic variants effect on the protein structure. Three novel variants were identified in three genes “MFSD8 (CLN7) , AGTPBP1 , and APTX” and other previously reported three variants have been detected in “ TPP1 , AGTPBP1 and PCDHGC4” genes. In this cohort, we described the detailed unique phenotypic characteristics in view of the identified genetic profile in patients with ND disorders, hence expanding the mutational spectrum of such disorders.