PMC5088547_01
(a) Pedigree and findings of COL4A5 mutation in two patients. The arrow indicates the proband. Unaffected individuals with kidney diseases are denoted by empty squares (men) and circles (women). Affected individuals with X-linked Alport syndrome are denoted by blackened circles (patients 1 and 2). Affected individuals with biopsy-unproven kidney disease are denoted by striped circles. Genetic analyses revealed that both patients had a heterozygous mutation (c. 2,767G>C) in exon 32. (b) X chromosome inactivation assays for our patients. In methylation-sensitive enzymes, a methylated allele is inactivated and cannot be digested by HpaII. Patient 1 and 2 both showed a random pattern with ratios of 77: 23 and 31: 69, respectively. It was impossible to distinguish whether the mutated allele was possessed by an activated or inactivated X chromosome because both had the same number of CAG repeats.
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The pedigree of her family is shown in Fig. 1a. The analysis revealed that both patients had a heterozygous mutation (c.2767G>C) in exon 32 (Fig. 1a). To investigate X chromosome inactivation, the human androgen receptor (HUMARA) assay was performed in both patients. The HUMARA assay for patients 1 and 2 revealed that the X chromosome inactivation pattern was 77:23 and 31:69, respectively (Fig. 1b).
Renal biopsy findings in X-linked Alport syndrome with a novel mutation. Patient 1 shows (a) a normal pattern of the alpha 2 chain of type IV collagen in the GBM and (b) segmental and mosaic patterns of the alpha 5 chain of type IV collagen in the GBM and the absence of staining in Bowman's capsule and the TBM. (c) The merged findings of the alpha 2 and 5 chains of type IV collagen are shown. (d) Electron microscopy reveals a split lamina densa (arrows) and thin GBM. Patient 2 shows (e) a normal pattern of the alpha 2 chain of type IV collagen in the GBM and (f) a mosaic pattern of the alpha 5 chain of type IV collagen in the GBM and TBM. (g) The merged findings of the alpha 2 and 5 chains of type IV collagen are shown. (h) Electron microscopy reveals a split lamina densa (arrow). GBM: glomerular basement membrane, TBM: tubular basement membrane
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The renal biopsy findings of the two patients are shown in Fig. 2.