title: Analysis of phenotype, enzyme activity and genotype of Chinese patients with POMT1 mutation.
abstract: Protein O-mannosyltransferase 1 (POMT1) is a glycosyltransferase involved in α-dystroglycan glycosylation. POMT1 mutations cause a wide spectrum of clinical conditions from Walker-Warburg syndrome (WWS), which involves muscle, eye and brain abnormalities, to mild forms of limb-girdle muscular dystrophy with mental retardation. We aimed to elucidate the impact of different POMT1 mutations on the clinical phenotype. We report five Chinese patients with POMT1 mutations: one had a typical clinical manifestation of WWS, and the other four were diagnosed with congenital muscular dystrophy with mental retardation of varying severity. We analyzed the influence of the POMT1 mutations on POMT activity by assaying the patients' muscles and cultured skin fibroblasts. We demonstrated different levels of decreased POMT activity that correlated highly with decreased α-dystroglycan glycosylation. Our results suggest that POMT activity is inversely proportional to clinical severity, and demonstrate that skin fibroblasts can be used for differential diagnosis of patients with α-dystroglycanopathies. We have provided clinical, histological, enzymatic and genetic evidence of POMT1 involvement in five unrelated Chinese patients.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Haipo
authors.initials: H
authors.lastname: Yang
authors.affiliation: Molecular Glycobiology, Research Team for Mechanism of Aging, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Manya
authors.affiliation: Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiao
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Radiology, Peking University First Hospital, Beijing, China.
authors.forename: Jiangxi
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Child Ophthalmology, Peking University First Hospital, Beijing, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
authors.affiliation: Molecular Glycobiology, Research Team for Mechanism of Aging, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
authors.forename: Tamao
authors.initials: T
authors.lastname: Endo
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Xiru
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiong
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004452:Echocardiography; D004789:Enzyme Activation; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D008364:Mannosyltransferases / Q000235:genetics* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase