title: Dystroglycanopathy with two novel POMT1 mutations in a Chinese boy with developmental delay and muscular dystrophy.
abstract: Alpha-dystroglycanopathies are a group of diseases due to reduced glycosylation of alpha-dystroglycan, which commonly result from mutations in POMT1, POMT2, and POMGnT1. Patients with alpha-dystroglycanopathies present with muscular, cerebral, and ocular involvements with differing severities. We reported a boy who presented with muscular dystrophy, developmental delay, and non-specific white matter lesions. Mutation analysis of POMT1 was performed and revealed two novel mutations, a substitution mutation (c.176T>G) and a duplication mutation (c.2059dupC) which results in premature termination of translation. In-silico prediction in five different platforms concurred that the substitution is damaging, and functional studies by immunofluorescence revealed lack of staining in the carbohydrate moiety of alpha-dystroglycan, confirming the molecular findings in a functional manner. In conclusion, we reported the first case of genetically confirmed alpha-dystroglycanopathy due to mutations in POMT1 in Chinese.
authors.affiliation: Genetic Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong Special Administrative Region.
authors.forename: Yeow Kuan
authors.initials: YK
authors.lastname: Chong
authors.affiliation: Department of Paediatrics, United Christian Hospital, Hong Kong Special Administrative Region.
authors.forename: Louis Che Kwan
authors.initials: LC
authors.lastname: Ma
authors.affiliation: Department of Diagnostic Radiology and Organ Imaging, United Christian Hospital, Hong Kong Special Administrative Region.
authors.forename: Kit Lin
authors.initials: KL
authors.lastname: Lo
authors.affiliation: Department of Pathology, United Christian Hospital, Hong Kong Special Administrative Region.
authors.forename: Clary Ka Lai
authors.initials: CK
authors.lastname: Lee
authors.affiliation: Genetic Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong Special Administrative Region.
authors.forename: Chloe Miu
authors.initials: CM
authors.lastname: Mak
authors.affiliation: Department of Pathology, Queen Mary Hospital, Hong Kong Special Administrative Region.
authors.forename: Amanda Nim Chi
authors.initials: AN
authors.lastname: Kan
authors.affiliation: Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region. Electronic address: ching-wanlam@pathology.hku.hk.
authors.forename: Ching Wan
authors.initials: CW
authors.lastname: Lam
mesh_terms: D001921:Brain / Q000473:pathology; D002648:Child; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000150:complications* / Q000235:genetics*; D049030:Dystroglycans / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008364:Mannosyltransferases / Q000235:genetics*; D009136:Muscular Dystrophies / Q000150:complications* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*
chemical_list: C483081:DAG1 protein, human; D049030:Dystroglycans; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase
keywords: Dystroglycans; Muscular dystrophies; Protein-O-mannosyltransferase