Genetic Analysis For A Family With Limb-Girdle Muscular Dystrophy

Objective:To study the clinical and genotype of limb-girdle muscular dystrophy (LGMD), and analysis the possible genes related to the pathogenesis of LGMD.Method:Two brothers in this family were suffered from muscular disorder with onset at 30-years old. Their clinical manifestations are similar with proximal muscle weakness and atrophy on extremities. DNA of the family members were extracted from peripheral blood samples, and genetic testing of LGMD1A, LGMD1B, LGMD1C, DYSF, LGMD1F and TTN gene were performed by polymerase chain reaction (PCR) and direct sequencing.Result:Genetic test results of both brothers:three anomalies found in DYSF gene:exon22 c.1827T>C(Asp809Asp)、exon40 c.4008C>A(Ile1336Ile) and exon23 c.2025G>A (Gln675Gln), one anomaly found in LGMD1B gene: exon10 C.1698C>T (His566His), two anomalies found in LGMD1F:exon6 C.759C>G (Leu253Leu) and exon21 c.2661C>T (Ala887Ala). However, all six mutations are nonsense mutation. No abnormality was found in both LGMD1A and LGMDIC genes. This family also had TTN gene testing. Missense mutation c.63065G>A (Arg21022His) was detected only in the proband’s brother Ⅱ-2, while the sequence of his mother and the proband (Ⅱ-1) of this site were normal.Conclusion:1. Six nonsense mutations of DYSF, LGMD1B and LGMD1F genes, and one missense mutation of TTN gene were detected in this family. The pathogenes of LGMD pedigree is more complex, and associated with a plurality of gene mutations.2. LGMD is muscular disease with genetic and clinical heterogeneity.