PMC8365467_01
The clinic and sequencing data of this FSGS family. (A) The pedigree of this FSGS family. Squares indicate male family members; circles, female members; black symbols, the affected members; white symbols, unaffected members; arrow, proband. (B) HE staining (C) Masson staining for renal biopsy of the proband (IV-1). (D) Sanger DNA sequencing chromatogram demonstrates a heterozygosity mutation (c.1734_1735insG/p.K579Efs*7) of CD2AP gene in affected members. (E) Alignment of multiple CD2AP protein sequences across species. Letters in red show the K579 site is evolutionarily conserved.
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F1
Masson staining mesangial area showed mesophilic deposition (Figures 1B,C). Co-segregation analysis shown that only a previously not described heterozygous mutation (c.1734_1735insG/p.K579Efs*7) in exon 16 of the CD2AP gene was observed in all three affected patients (III-3, III7, and IV-1) and excluded in the healthy members (Figure 1D). Family screening showed that the frameshift mutation was inherited via the paternal allele (Figure 1A). Alignment of CD2AP amino acid sequences revealed the affected amino acid was evolutionarily conserved (Figure 1E).
The bioinformatics analysis of mutations. (A) Structure prediction of the mutant protein. The wild type CD2AP (CD2AP-WT) protein structure and the p.K579Efs*7 mutant CD2AP (CD2AP-p.K579Efs*7) protein structure were predicted by SWISS-MODEL online software. (B) Overview of all known and novel CD2AP mutations. The CD2AP gene is shown, with all known CD2AP mutations (black letters) and novel mutation (red letters). Blue rectangles indicate exons. Introns are not shown to scale. The CD2AP protein structure is shown. CC, coiled-coil domain; SH3, Src homology 3 domain.
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F2
As the results showed, a loss of almost all of the C-terminal in the K579Efs*7 mutated CD2AP protein was observed, in comparison with the wild type, as marked by the red frame in the figure (Figure 2A).