A novel variant of GALC in a familial case of Krabbe disease:Insights from structural bioinformatics and molecular dynamics simulation

作     者：Ikram Ullah Muhammad Waqas Muhammad Ilyas Sobia Ahsan Halim Akmal Ahmad Natalia Dominik Wahid Ullah Muhammad Abbas Muhammad Aamir Henry Houlden Stephanie Efthymiou Ajmal Khan Ahmed Al-Harrasi Ikram Ullah;Muhammad Waqas;Muhammad Ilyas;Sobia Ahsan Halim;Akmal Ahmad;Natalia Dominik;Wahid Ullah;Muhammad Abbas;Muhammad Aamir;SYNaPS Study Group;Queen Square Genomics;Henry Houlden;Stephanie Efthymiou;Ajmal Khan;Ahmed Al-Harrasi

作者机构：Centre for Omic SciencesIslamia College University PeshawarPeshawarKhyber Pakhtunkhwa 25120Pakistan Department of Biotechnology and Genetic EngineeringHazara UniversityMansehraDhodial 21120Pakistan Natural and Medical Sciences Research CenterUniversity of NizwaNizwa 616Sultanate of Oman Department of BioengineeringUniversity of Engineering and Applied SciencesSwatKhyber Pakhtunkhwa 19060Pakistan Department of Neuromuscular DisordersUCL Queen Square Institute of NeurologyLondon WC1N 3BGUnited Kingdom 

出 版 物：《Genes & Diseases》 (基因与疾病(英文))

年 卷 期：2023年第10卷第6期

页      面：2263-2266页

核心收录：

学科分类：0710[理学-生物学] 0303[法学-社会学] 03[法学] 030302[法学-人口学] 

基　　金：funded by the Higher Education Comission of Pakistan(No.NRPU-20–17341) 

主　　题：dynamics birth GAL 

摘      要：Krabbe disease or globoid cell leukodystrophy(GLD;MIM#245200)is a rare and fatal lysosomal storage disease with an autosomal recessive mode of inheritance that results from the deficiency of galactocerebrosidase(GALC;E.C.3.***.1.46),a lysosomal enzyme encoded by the GALC gene.1 GALC breaks down galactosylceramide,a cerebroside located mainly in the myelin *** in GALC cause the accumulation of a cytotoxic metabolite,galactosylsphingosine or psychosine,which can be toxic to oligodendrocytes and Schwann cells.2 The failure to digest galactosylceramide triggers the formation of multi-nucleated globoid cells,causing severe demyelination,axonopathy,and neuronal death.3 The reported frequency of Krabbe disease is 1 in 100,000 live births with symptoms including irritability,loss of motor ability,spasticity,ataxia,visual dysfunction,seizures,andcognitive impairment.