The Diagnostic Value of Whole-Exome Sequencing in a Spectrum of Rare Neurological Disorders Associated with Cerebellar Atrophy

Molecular Neurobiology - Trang 1-13 - 2023
Engy A. Ashaat1, Hoda A. Ahmed2, Nesma M. Elaraby2, Alaaeldin Fayez3, Ammal M. Metwally4, Mona K. Mekkawy5, Dalia Farouk Hussen5, Neveen A. Ashaat6, Rasha M. Elhossini1, Heba Ahmed ElAwady7, Randa H. A. Abdelgawad8, Mona El Gammal1, Mohamed Ahmed Al Kersh9, Dina Amin Saleh10
1Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt
2Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt
3Molecular Genetics and Enzymology Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt
4Community Medicine Research Department/ Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt
5Human Cytogenetic Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt
6Human Genetics, Ain Shams University, Cairo, Egypt
7Pediatrics Department, Fayoum University Hospitals, Faiyum, Egypt
8Ophthalmology department, Ain Shams University, Cairo, Egypt
9Orthopedic Department, Ain Shams University, Cairo, Egypt
10Pediatric Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Tóm tắt

Several neurological disorders, neurodevelopmental disorders, and neurodegenerative disorders have a genetic element with various clinical presentations ranging from mild to severe presentation. Neurological disorders 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. The cerebellum might be involved at any time, either during development and maturation or later in life. Herein, we describe a spectrum of NDDs and NDs in seven patients from six Egyptian families. The core clinical and radiological features of our patients included dysmorphic features, neurodevelopmental delay or regression, gait abnormalities, skeletal deformities, visual impairment, seizures, and cerebellar atrophy. Previously unreported clinical phenotypic findings were recorded. Whole-exome sequencing (WES) was performed followed by an in silico analysis of the detected genetic variants’ effect on the protein structure. Three novel variants were identified in three genes MFSD8, 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 given the identified genetic profile in patients with neurological “neurodevelopmental disorders and neurodegenerative disorders” disorders associated with cerebellar atrophy, hence expanding the mutational spectrum of such disorders.

Tài liệu tham khảo

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