PMC6354032_01
(A) Pedigree of the present family, segregating autosomal recessive form of LGMD2F. Clear circles and squares represent normal females and males, respectively. Black symbol represents the affected individual (proband). Double lines indicate consanguineous union. Individual numbers labeled with asterisks, indicate those who were available for the present study. (B) Affected individual's (IV-1) hand showing contractures. (C,D) Right foot of the affected individual (IV-1) showing fixed flection deformity and stiffness of the toes. (E) Feet showing the weakness in the gastrocnemius muscle and the inability to stand without support.
fgene-09-00727-g001.jpg
PMC6354032_01_fgene-09-00727-g001.jpg
F1
The present study describes a single affected boy (IV-1; 11 years) that belongs to a consanguineous Pakistani family (Figure 1A). He has relatively normal extensor muscles of the fingers, wrist, toes flexors and hip abductors, with severe weakness of other muscles (Figures 1B-E).
Schematic representation of exons and protein product of SGCD gene. (A,B) Arrows show the position the mutation (c.289C>T; p.Arg97*) identified in the present study. (C) Conservation of the Arg (R) 97 amino acid across different species. Notably, the nonsense mutation (c.298C>T) results in a premature stop codon (TCA). (D) Schematic representation of the sarcoglycan complex. The intracellular and extracellular regions of sarcoglycans are separated by a cell membrane. Different sarcoglycans, alpha, beta, gamma, delta, dysferlin, caveolin 3, dystrophin and laminin are shown and associated disorders are also shown using arrows.
fgene-09-00727-g002.jpg
PMC6354032_01_fgene-09-00727-g002.jpg
F2
Following step-by-step filtering process for screening homozygous and compound heterozygous variants in the known genes causing LGMDs, a nonsense mutation (c.289C>T; p.Arg97*) was identified in the exon 3 of the SGCD gene, located on chromosome 5q33.2-q33.3 (Figures 2A,B).