ClinVar

In a German family with Duchenne-like muscular dystrophy of intermediate severity (LGMDR3; 608099), Piccolo et al. (1995) found a homozygous CGC-to-TGC transition in exon 3 of the SGCA gene, resulting in an arg77-to-cys (R77C) substitution. The same mutation was found in the heterozygous state in 2 apparently unrelated French families in which the affected individuals were compound heterozygotes. In a note added in proof, Piccolo et al. (1995) commented that out of a total of 46 mutated chromosomes from unrelated families in Europe and the US, 11 had the R77C mutation. Four patients were homozygous for the mutation.

Passos Bueno et al. (1995) identified the same mutation in 3 Brazilian families with a relatively mild form of LGMD2D.

In a Japanese patient with autosomal recessive childhood-onset muscular dystrophy from a consanguineous family, Kawai et al. (1995) found homozygosity for the R77C mutation. Muscle biopsy showed complete absence of adhalin.

Bartoli et al. (2008) found that SGCA with the R77C mutation was retained in the endoplasmic reticulum (ER), where it formed aggregates. Surface expression of mutant SGCA could be rescued by inhibiting its degradation via proteasome-mediated ER-associated degradation (ERAD) or by inhibiting mannosidase I (MAN1B1; 604346), an ER enzyme that directs misfolded glycoproteins toward ERAD.