case_images: PMC10937461_01
case_images: The clinical and genetic analysis of the family with congenital cataracts. (A) Pedigree of the family. White circles/squares are unaffected family members, and the arrow indicates the proband. (B) The right eye of the proband. (C) Schematic representation of the filter strategies employed in our study. (D) Sanger DNA sequencing chromatogram demonstrates the heterozygosity for an MAF missense mutation (c.901T>C/p.Y301H) in the family.
case_images: fmed-11-1332992-g001.jpg
case_images: PMC10937461_01_fmed-11-1332992-g001.jpg
case_images: fig1
case_images: Here, we enrolled the family from Hebei province, China (Figure 1A). The affected proband, a four-year-old boy was admitted to Hebei General Hospital and diagnosed as a total congenital cataract of the right eye (Figure 1B). After the abovementioned data filtering and Sanger sequencing validation (Figure 1C), a new mutation (NM_005360, c.901T>C/p.Y301H) of MAF was discerned in the proband (Table 1). Co-segregation analysis indicated that the new mutation was present in the affected family members and was not detected in unaffected family members and healthy controls as well as 200 local control cohorts (Figure 1D).
case_images: The bioinformatics analysis of the MAF p.Y301H mutation. (A) Alignment of multiple MAF protein sequences across species. The Y301-affected amino acid is located in the highly conserved amino acid region in different mammals (from Ensembl). The red column shows the Y301 site. Blue square: transactivation domain. Red square: extended homology region. Orange square: basic region motif. Green square: leucine zipper motif. (B) The hydrophobic surface area and surface charge of the WT and mutated MAF were predicted by SWISS-MODEL and alphafold2. The red arrow and red square indicate the differences between WT and mutated protein.
case_images: fmed-11-1332992-g002.jpg
case_images: PMC10937461_01_fmed-11-1332992-g002.jpg
case_images: fig2
case_images: Cross-species alignment analysis of MAF amino acid sequences revealed that this mutated site was highly evolutionarily conserved (Figure 2A). Swiss-Model and alphafold2 online software found that the p.Y301H mutation changed the surface hydrophobic area and surface charge of MAF (Figure 2B).