PMC2622714_01
Corneal phenotype of the affected family members with ACD due to an R124H mutation in TGFBI. A: Preoperative photograph of the right eye of proband revealed grayish spot-like confluent opacities presented in the anterior stroma and covering almost the entire cornea. B: Corneal examination of the left eye of I1 (father of the proband) showed several distinct granular deposits in the superficial stroma of the central cornea (arrows). C and D: Multiple granular deposits and a few confluent opacities were observed in the anterior stroma of central cornea in both right eyes of III2 and III5, respectively.
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Slit-lamp examination showed several distinct granular deposits in superficial stroma of the central cornea (Figure 2B). Multiple granular deposits and a few confluent opacities were observed in the anterior stroma of central cornea (Figure 2C,D).
PMC2622714_02
Corneal phenotype of the affected family members with ACD due to an R124H mutation in TGFBI. A: Preoperative photograph of the right eye of proband revealed grayish spot-like confluent opacities presented in the anterior stroma and covering almost the entire cornea. B: Corneal examination of the left eye of I1 (father of the proband) showed several distinct granular deposits in the superficial stroma of the central cornea (arrows). C and D: Multiple granular deposits and a few confluent opacities were observed in the anterior stroma of central cornea in both right eyes of III2 and III5, respectively.
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Slit-lamp examination showed several distinct granular deposits in superficial stroma of the central cornea (Figure 2B). Multiple granular deposits and a few confluent opacities were observed in the anterior stroma of central cornea (Figure 2C,D).
Sequence analysis of TGFBI exon 4 in this family. A: A normal sequence is shown, which encodes arginine in codon 124. B: The proband had homozygous substitutions at nucleotide position c.371G>A, which results in a arginine to histidine acid substitution (R124H). C: The proband's father had a heterozygous mutation of R124H at the same position.
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II3 and II4 (Figure 3B).The variation lies in exon 4 and results in a arginine to histidine acid substitution at the protein level (R124H). In addition, 4 affected (I1, II5, III2, and III5) and 7 unaffected (II1, II6, III6, III7, III9, III10, and III11)family members carrying the same variation in the heterozygous state were identified(Figure 3C) .
Histopathological features of affected cornea from the right eye of the proband carrying the homozygous TGFBI R124H mutation at the age of 43. The visual acuity of the proband before penetrating keratoplasty was 20 cm/CF. A: Light microscopy of excised corneal tissue stained with congo red revealed variably sized and irregularly shaped deposits of amyloid material, predominantly in the anterior and middle stroma (arrows). B: The deposits stained with Masson's trichrome showed brightly red accumulation of hyaline under the Bowman's membrane (arrows). The epithelium showed focal areas of dehiscence from Bowman's membrane.
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The deposits stained positively with congo red in the anterior and middle stroma indicating be amyloid (Figure 4A) and staining with Masson's trichrome showed bright red accumulation of hyaline under Bowman's membrane (Figure 4B). In addition, the epithelium showed focal areas of dehiscence from Bowman's membrane (Figure 4B).