Case Report Genetic Analysis of Undiagnosed Juvenile GM1-Gangliosidosis by Microarray and Exome Sequencing Ahmed Bouhouche , 1,2 Houyam Tibar, 1 Yamna Kriouale, 3 Mohammed Jiddane, 4 Imane Smaili , 1 Naima Bouslam, 1 Ali Benomar, 1,2 Mohamed Yahyaoui, 1 and Elmostafa El Fahime 2,5 1 Research Team in Neurology and Neurogenetics, Genomics Center of Human Pathologies, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat, Morocco 2 Genetics Center of the Cheikh Zayed Foundation, Abulcasis International University of Health Sciences, Rabat, Morocco 3 Department of Neuropediatrics and Metabolism Diseases, Hˆ opital d’Enfant, CHU Ibn Sina, Rabat, Morocco 4 Department of Neuroradiology, Hˆ opital des Sp´ ecialit´ es, CHU Ibn Sina, Rabat, Morocco 5 Assistance Units for Scientifc and Technical Research (UATRS), National Center for Scientifc and Technical Research (CNRST), Rabat, Morocco Correspondence should be addressed to Ahmed Bouhouche; a.bouhouche@um5s.net.ma Received 3 September 2018; Accepted 5 November 2018; Published 15 November 2018 Academic Editor: Monika Dmitrzak-Weglarz Copyright © 2018 Ahmed Bouhouche et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. GM1 gangliosidosis is an autosomal recessive lysosomal storage disorder due to mutations in the lysosomal acid 3-galactosidase gene, GLB1. It is usually classifed into three forms, infantile, juvenile, or adult, based on age at onset and severity of central nervous system involvement. Because of their broad clinical spectrum and their similarity to many other aetiologies, including inherited neurodegenerative and metabolic diseases, it is ofen difcult to diagnose such diseases. Recently, whole exome sequencing (WES) has become increasingly used when a strong hypothesis cannot be formulated based on the clinical phenotype. Here, we present three patients belonging to a consanguineous Moroccan family with a GM1-gangliosidosis with unusual clinical onset and atypical radiological presentation that had eluded diagnosis for over a decade. To identify the disease-causing mutation, we performed a whole exome sequencing and a chromosomal microarray genotyping in order to reduce the number of genetic variants to be interpreted, by focusing the data analysis only on the linked loci. Te already known pathogenic missense mutation c.601G>A in GLB1 (p.R201C) was found at homozygous state in the proband V.1 and at heterozygous state in his father IV.1. Te mutation was validated by Sanger sequencing and segregated in all the family members according to a recessive mode of inheritance. Outside of the linked loci, we found the EXOSC8 p.Ser272Tr mutation at heterozygous state in all the patients and their mother IV.2. Tis mutation was reported to cause pontocerebellar hypoplasia type 1C and could act as a modifying factor that exacerbates the brain atrophy of patients. Our study identifed the frst GLB1 mutation in North Africa in patients with unexpected brain-MRI outcomes extending the clinical spectrum of the GM1-gangliosidosis. 1. Introduction GM1 gangliosidosis is an autosomal recessive storage disor- der, which occurs in 1 per 100,000 to 200,000 newborns [1]. It is caused by a defciency of beta-galactosidase (GLB1), a lysosomal hydrolase that may be defective with respect to ker- atan sulfate in Morquio B disease (MBD) or to gangliosides, lactosylceramide, asialofetuin, and oligosaccharides carrying terminal beta-linked galactose and keratan sulfate in GM1- gangliosidosis [2]. Tis defciency leads to the accumulation of keratan sulfate, glycolipids, and GM1 gangliosides in diferent tissues, especially in peripheral and central nervous system [3]. Tis disease can be divided into 3 clinical forms (type I, type II, and type III) based on the age of onset and the severity of the phenotype. Hindawi Case Reports in Genetics Volume 2018, Article ID 8635698, 8 pages https://doi.org/10.1155/2018/8635698