Concomitant Alpha- and Gamma-Sarcoglycan Deficiencies in a Turkish Boy with a Novel Deletion in the Alpha-Sarcoglycan Gene

Abstract

Limb-girdle muscular dystrophy type 2D (LGMD-2D) is caused by autosomal recessive defects in the alpha-sarcoglycan gene located on chromosome 17q21. In this study, we present a child with alpha-sarcoglycanopathy and describe a novel deletion in the alpha-sarcoglycan gene. A 5-year-old boy had a very high serum creatinine phosphokinase level, which was determined incidentally, and a negative molecular test for the dystrophin gene. Muscle biopsy showed dystrophic features. Immunohistochemistry showed that there was diminished expression of alpha- and gamma-sarcoglycans. DNA analysis revealed a novel 7 bp homozygous deletion in exon 3 of the alpha-sarcoglycan gene. His parents were consanguineous heterozygous carriers of the same deletion. We believe this is the first confirmed case of primary alpha-sarcoglycanopathy with a novel deletion in Turkey. In addition, this study demonstrated that both muscle biopsy and DNA analysis remain important methods for the differential diagnosis of muscular dystrophies because dystrophinopathies and sarcoglycanopathies are so similar.

Sarcolemmal deficiency of sarcoglycan complex in an 18-month-old Turkish boy with a large deletion in the beta sarcoglycan gene

“…Bonnemann et al . [ 4 ] also determined that the total loss of sarcolemmal SGCs was caused by defects in the SGCB gene.Therefore they recommended using antibodies against all four SGCs for immune analysis of skeletal muscle sections [ 1 , 4 , 7 , 8 , 12 ]. Similarly, a concomitant reduction in dystrophin and any of the SGCs may illustrate the importance of considering coexisting dystrophinopathies in patients with sarcoglycandeficient LGMD [ 1 - 3 ].…”

“…Complex mechanisms have been postulated for the development of the clinical heterogenity of LGMD-2E. A mutation in any SGC gene can lead to a reduction of the other SGCs [ 4 - 8 ]. The sarcoglycan-sarcospan and dystroglycan complexes were disrupted in skeletal, cardiac and smooth muscle membranes.…”

Combined use of genetic and immunohistochemical analysis is a critical step in differential diagnosis of sarcoglycanopathies

“…After this report, we have also diagnosed 19 new patients (3 siblings) with LGMD. Interestingly some of these patients presented with multiple sarcoglycan defects (8)(9)(10) . In addition, dystrophin gene mutations were determined in a sibling who demonstrated permanent gamma-sarcoglycan deficiency with normal dystrophin expression as detected on the histopathological examination of the muscle biopsy specimen (Table 1).…”

“…Probably, many male patients with LGMD might be underestimated, and these patients might be misdiagnosed as having DMD or BMD (8)(9)(10) . If these patients can be subjected to appropriate immunohistochemical examinations and molecular analysis, then normal staining pattern of dystrophin can be revealed, and an autosomal recessive mode of inheritance can be disclosed.…”

“…In summary, as an important corollary not only the primarily deficient SGC gene, but also all related genes should be analyzed. Besides, patterns of genetic complexity associated with LGMDs should be considered in the differential diagnosis of muscular dystrophies (2,4,(8)(9)(10)13) .…”