title: A slowly progressive form of limb-girdle muscular dystrophy type 2C associated with founder mutation in the SGCG gene in Puerto Rican Hispanics.
abstract: Limb-girdle muscular dystrophy type 2C (LGMD2C) is considered one of the severe forms of childhood-onset muscular dystrophy. The geographical distribution of founder mutations in the SGCG gene has a prominent effect on the prevalence of LGMD2C in certain populations. The aim of this study was to confirm the hypothesis that the c.787G>A (p.E263K) mutation in the SGCG gene is a founder mutation among Puerto Rican Hispanics and to characterize the associated clinical and immunohistochemical phenotype. Genotyping of six polymorphic microsatellite markers internal to (D13S232) and flanking (D13S175, D13S292, D13S787, D13S1243, D13S283) the SGCG gene was performed on four unrelated Puerto Rican patients with LGMD2C. Preserved ambulation to the second decade of life was observed in at least two subjects. Immunostaining of skeletal muscle demonstrated absence of γ-sarcoglycan in all affected subjects. Two markers, D13S232 and D13S292, were highly informative and confirmed that all four families share the haplotype of the mutant allele. Our findings confirm that the E263K missense mutation in the SGCG gene is a founder mutation in Puerto Rican Hispanics. A slowly progressive disease course with prolonged preservation of ambulation can be seen in association with this mutation, providing evidence for phenotypic variability.
authors: Center for Gene Therapy and Paul D. Wellstone Muscular Dystrophy Research Center, Nationwide Children's Hospital Columbus, Ohio ; Department of Pediatrics and Neurology, The Ohio State University Columbus, Ohio.
authors: Samiah A
authors: SA
authors: Al-Zaidy
authors: Center for Gene Therapy and Paul D. Wellstone Muscular Dystrophy Research Center, Nationwide Children's Hospital Columbus, Ohio.
authors: Vinod
authors: V
authors: Malik
authors: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital Columbus, Ohio.
authors: Kelley
authors: K
authors: Kneile
authors: Center for Gene Therapy and Paul D. Wellstone Muscular Dystrophy Research Center, Nationwide Children's Hospital Columbus, Ohio ; Department of Pediatrics and Neurology, The Ohio State University Columbus, Ohio.
authors: Xiomara Q
authors: XQ
authors: Rosales
authors: Center for Gene Therapy and Paul D. Wellstone Muscular Dystrophy Research Center, Nationwide Children's Hospital Columbus, Ohio.
authors: Ana Maria
authors: AM
authors: Gomez
authors: Center for Gene Therapy and Paul D. Wellstone Muscular Dystrophy Research Center, Nationwide Children's Hospital Columbus, Ohio ; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital Columbus, Ohio.
authors: Sarah
authors: S
authors: Lewis
authors: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital Columbus, Ohio.
authors: Sayaka
authors: S
authors: Hashimoto
authors: Department of Pathology, Ohio State University and Nationwide Children's Hospital Columbus, Ohio ; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital Columbus, Ohio.
authors: Julie
authors: J
authors: Gastier-Foster
authors: Department of Neurology, Boston Children's Hospital and Harvard Medical School Boston, Massachusetts.
authors: Peter
authors: P
authors: Kang
authors: Department of Neurology, Boston Children's Hospital and Harvard Medical School Boston, Massachusetts.
authors: Basil
authors: B
authors: Darras
authors: Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital Boston, Massachusetts.
authors: Louis
authors: L
authors: Kunkel
authors: Department of Neurology, School of Medicine, University of Puerto Rico San Juan, Puerto Rico.
authors: Jose
authors: J
authors: Carlo
authors: Center for Gene Therapy and Paul D. Wellstone Muscular Dystrophy Research Center, Nationwide Children's Hospital Columbus, Ohio ; Department of Pediatrics and Neurology, The Ohio State University Columbus, Ohio.
authors: Zarife
authors: Z
authors: Sahenk
authors: Department of Pathology, The University of Iowa Carver College of Medicine Iowa City, Iowa.
authors: Steven A
authors: SA
authors: Moore
authors: Department of Pathology, Ohio State University and Nationwide Children's Hospital Columbus, Ohio ; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital Columbus, Ohio.
authors: Robert
authors: R
authors: Pyatt
authors: Center for Gene Therapy and Paul D. Wellstone Muscular Dystrophy Research Center, Nationwide Children's Hospital Columbus, Ohio ; Department of Pediatrics and Neurology, The Ohio State University Columbus, Ohio ; Department of Pathology, Ohio State University and Nationwide Children's Hospital Columbus, Ohio.
authors: Jerry R
authors: JR
authors: Mendell
keywords: Founder mutation; LGMD2C; Puerto Rico; SGCG; gamma-sarcoglycan