Journal article
A slowly progressive form of limb‐girdle muscular dystrophy type 2C associated with founder mutation in the SGCG gene in Puerto Rican Hispanics
Molecular genetics & genomic medicine, Vol.3(2), pp.92-98
03/2015
DOI: 10.1002/mgg3.125
PMCID: PMC4367081
PMID: 25802879
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.
In this report, we describe four unrelated LGMD2C patients of Hispanic descent from the island of Puerto Rico that share a E263K (G787A) mutation within exon 8 of the SGCG gene. A slowly progressive phenotype with prolonged preservation of ambulation is illustrated in two of our patients. We also confirmed the founder effect of this mutation among Puerto Rican Hispanics using linkage analysis and determined that this mutation in affected individuals segregates with alleles inherited from each parent.
Details
- Title: Subtitle
- A slowly progressive form of limb‐girdle muscular dystrophy type 2C associated with founder mutation in the SGCG gene in Puerto Rican Hispanics
- Creators
- Samiah A Al‐Zaidy - The Ohio State UniversityVinod Malik - Nationwide Children's HospitalKelley Kneile - Nationwide Children's HospitalXiomara Q Rosales - The Ohio State UniversityAna Maria Gomez - Nationwide Children's HospitalSarah Lewis - Nationwide Children's HospitalSayaka Hashimoto - Nationwide Children's HospitalJulie Gastier‐Foster - Nationwide Children's HospitalPeter Kang - Boston Children's Hospital and Harvard Medical SchoolBasil Darras - Boston Children's Hospital and Harvard Medical SchoolLouis Kunkel - Boston Children's HospitalJose Carlo - University of Puerto RicoZarife Sahenk - The Ohio State UniversitySteven A Moore - The University of Iowa Carver College of MedicineRobert Pyatt - Nationwide Children's HospitalJerry R Mendell - Ohio State University and Nationwide Children's Hospital
- Resource Type
- Journal article
- Publication Details
- Molecular genetics & genomic medicine, Vol.3(2), pp.92-98
- DOI
- 10.1002/mgg3.125
- PMID
- 25802879
- PMCID
- PMC4367081
- NLM abbreviation
- Mol Genet Genomic Med
- ISSN
- 2324-9269
- eISSN
- 2324-9269
- Number of pages
- 7
- Grant note
- NIMHD, NIH (8U54MD007587) NIH Wellstone Muscular Dystrophy Cooperative Research Center (U54; NS053672) National Institutes of Health (NIH) Ruth L. Kirschstein T32 Research Training Grant NIH (R01NS080929)
- Language
- English
- Date published
- 03/2015
- Academic Unit
- Pathology
- Record Identifier
- 9984047640102771
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