case_images: PMC11764669_01
case_images: Sanger sequencing shows the c.781G>T mutation in a heterozygous state in the proband (a) and in a hemizygous state in the patient's brother (b). Each base corresponds to a color: red for Thymine, blue for Cytosine, yellow for Guanine, green for Adenine. K indicates the mutation in the heterozygous state as Thymine. Arrows indicate the mutation.
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case_images: PMC11764669_01_ijms-26-00473-g001.jpg
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case_images: In exon 5 of the gene, we identified the novel missense mutation c.781G>T (Figure 1a), which causes the substitution of a Glycine with a Cysteine at position 261 of the protein (p.G261C). In the samples of these two subjects, we identified the same novel mutation (in hemizygosis in the brother, Figure 1b), with almost null enzymatic activity in the male patient (0.7 nmol/mL/h), and of 1.8 nmol/mL/h in the female patient, with blood Lyso-Gb3 values of 29.9 nmol/L and 4.88 nmol/L, respectively (Table 1).
case_images: PMC11764669_02
case_images: Sanger sequencing shows the c.786G>T mutation in hemizygosity in the proband (a) and in heterozygosity in his mother (b). Each base corresponds to a color: red for Thymine, blue for Cytosine, yellow for Guanine, green for Adenine. K indicates that the mutation in heterozygosity is Thymine. Arrows indicate the mutation.
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case_images: PMC11764669_02_ijms-26-00473-g002.jpg
case_images: ijms-26-00473-f002
case_images: Tryptophan with a Cysteine at position 262 of the protein (p.W262C) (Figure 2a). The nucleotide variation c.786G>T has not been previously described in the literature and is not reported in Fabry disease-associated mutation databases, but determines the same amino acid substitution W262C that is instead reported as classic, and is associated with the mutation c.786G>A.
case_images: PMC11764669_03
case_images: Sanger sequencing shows the c.583insGAATA mutation in the heterozygous state in the proband. Each base corresponds to a color: red for Thymine, blue for Cytosine, yellow for Guanine, green for Adenine. Arrows indicate the insertion start point.
case_images: ijms-26-00473-g003.jpg
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case_images: ijms-26-00473-f003
case_images: Genetic analysis of the GLA gene allowed us to identify a five-nucleotide insertion (c.583insGAATA) in exon 4 of the gene (Figure 3), which causes slippage of the reading frame of translation, with the substitution of a Glycine with a Glutamic Acid at position 195 of the protein and the formation of a premature translation stop codon one nucleotide downstream from the mutation site (p.Gly195Glufs*1).
case_images: PMC11764669_04
case_images: Sanger sequencing shows the mutations c.621T>A (a) and c.427G>A (b) in the heterozygous state in the proband. Each base corresponds to a color: red for Thymine, blue for Cytosine, yellow for Guanine, green for Adenine. W and R indicate that the mutations in heterozygosity are Adenine. Arrows indicate the mutations.
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case_images: ijms-26-00473-f004
case_images: Genetic analysis of the GLA gene highlighted the novel nonsense mutation in exon 4 of the gene (c.621T>A) (Figure 4a): a change in a Thymine to an Adenine at position 621 of the GLA gene cDNA, which introduces a stop codon at position 207 of the polypeptide chain, generating a truncated protein (p.Y207X). A143T, a variant that has a conflicting pathogenicity classification, was also found (Figure 4b).