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case_images: (A) Atrophy of bilateral calves more pronounced distally giving a "stork leg" appearance akin to Charcot-Marie-Tooth disease. (B) Planovalgus deformities of both feet.
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case_images: Symmetric muscle atrophy of the calves was also noted, which he reported experiencing for as long as he could remember (Figure 1A). Additionally, it was noted that he had planovalgus deformities of both feet since the age of 5 years (Figure 1B), a condition similar to that of his uncle's feet.
case_images: Filtering steps for the variant calls in whole-exome sequencing.
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case_images: The remaining mutations were considered potential pathogenic mutations for further analysis (Figure 2). Genomic DNA was extracted from the patient's whole blood, and subsequent sequencing analysis identified a novel splice site mutation in intron 3 of SIGMAR1 gene (c.446-2A>T), which was further confirmed by Sanger sequencing (Figures 2, 3A).
case_images: (A) Splice site mutation in the SIGMAR1 identified in our patient. Sanger sequencing was performed using cDNA generated from the patient. (B) Mutation in the SIGMAR1 identified in our patient's mother. (C) Mutant pedigree map of familial mutations. Circles = females; squares = males; and slashes = deceased.
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case_images: Genomic DNA was extracted from the patient's whole blood, and subsequent sequencing analysis identified a novel splice site mutation in intron 3 of SIGMAR1 gene (c.446-2A>T), which was further confirmed by Sanger sequencing (Figures 2, 3A). SIGMAR1 variant as detected in the proband (Figure 3B). Subsequently, a pedigree analysis was performed (Figure 3C).
case_images: Mutation site of SIGMR1. The previously reported mutation site was located in exons and 3'-UTR, and the mutation site was located in intron.
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case_images: T) in the 3'-untranslated region in the FTLD-MND pedigree and mutations (c.304G > C, c.67231A > G, c.505 T > A, c.622C > T, c.283dupC, c.58 T > C, c.125 > G) in the SIGMAR1 gene in affected ALS patients. The phenotypes of each of these cases are presented in Table 1 and Figure 4.