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Clin Genet ; 81(6): 578-83, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21480868

RESUMO

The limb-girdle muscular dystrophies (LGMDs) are a heterogenous group of diseases characterized by shoulder-girdle and pelvic muscle weakness and wasting. LGMD 2E is an autosomal recessively inherited form of the disease caused by mutations in the ß-sarcoglycan (SGCB) gene located at 4q12. In this report, we describe a patient who demonstrates non-Mendelian inheritance of a homozygous missense mutation in SGCB resulting in disease expression. A combination of single-nucleotide polymorphism (SNP) array technology and microsatellite analysis revealed the occurrence of maternal uniparental disomy (UPD) for chromosome 4 in the patient. As a consequence of segmental isodisomy at 4q12, the patient inherited two identical SGCB alleles carrying a missense mutation predicted to result in abnormal protein function. SNP array technology proved to be an elegant means to determine the most probable mechanism of UPD formation in this case, and enabled us to determine the location of recombination events along chromosome 4. In our patient, UPD likely arose from a trisomy rescue event due to maternal meiotic non-disjunction that we speculate may have been caused by abnormal recombination at the pericentromeric region. Maternal UPD 4 is a rare finding, and to our knowledge this is the first reported case of UPD in association with LGMD.


Assuntos
Cromossomos Humanos Par 4/genética , Distrofia Muscular do Cíngulo dos Membros/genética , Polimorfismo de Nucleotídeo Único , Dissomia Uniparental/genética , Adulto , Feminino , Humanos , Masculino , Músculo Esquelético/metabolismo , Mutação , Análise Serial de Proteínas , Sarcoglicanas/genética
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