title: FKRP mutations, including a founder mutation, cause phenotype variability in Chinese patients with dystroglycanopathies.
abstract: Mutations in the fukutin-related protein (FKRP) gene have been associated with dystroglycanopathies, which are common in Europe but rare in Asia. Our study aimed to retrospectively analyze and characterize the clinical, myopathological and genetic features of 12 Chinese patients with FKRP mutations. Three patients were diagnosed with congenital muscular dystrophy type 1C (MDC1C) and nine patients were diagnosed with limb girdle muscular dystrophy type 2I (LGMD2I). Three muscle biopsy specimens had dystrophic changes and reduced glycosylated α-dystroglycan staining, and two showed reduced expression of laminin α2. Two known and 13 novel mutations were identified in our single center cohort. Interestingly, the c.545A>G mutation was found in eight of the nine LGMD2I patients as a founder mutation and this founder mutation in Chinese patients differs from the one seen in European patients. Moreover, patients homozygous for the c.545A>G mutation were clinically asymptomatic, a less severe phenotype than in compound heterozygous patients with the c.545A>G mutation. The 13 novel mutations of FKRP significantly expanded the mutation spectrum of MDC1C and LGMD2I, and the different founder mutations indicate the ethnic difference in FKRP mutations.
authors.affiliation: Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Fu
authors.affiliation: Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Haipo
authors.initials: H
authors.lastname: Yang
authors.affiliation: Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Cuijie
authors.initials: C
authors.lastname: Wei
authors.affiliation: Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiao
authors.affiliation: Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurology, Shenzhen Children's Hospital, Shenzhen, China.
authors.forename: Chunxi
authors.initials: C
authors.lastname: Han
authors.affiliation: Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Xiru
authors.initials: X
authors.lastname: Wu
authors.affiliation: Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiong
mesh_terms: D000293:Adolescent; D001706:Biopsy; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D018703:Founder Effect; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000235:genetics; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis / Q000235:genetics; D009154:Mutation; D010430:Pentosyltransferases; D010641:Phenotype; D011506:Proteins / Q000235:genetics*
chemical_list: D011506:Proteins; C443107:FKRP protein, human; D010430:Pentosyltransferases