Identification and Management of a Novel PRDM5 Gene Pathologic Variant in a Family With Brittle Cornea Syndrome.

PURPOSE: The aim of this study was to report a novel PRDM5 pathologic variant and ophthalmic findings in a family with 3 children diagnosed with brittle cornea syndrome (BCS). Histopathologic findings and surgical outcome of a child with BCS who underwent full-thickness corneal transplant are described. METHODS: This is an observational case report of a nonconsanguineous Laotian family with 3 siblings diagnosed with BCS. Data collected included visual acuity, cycloplegic refraction, slit-lamp biomicroscopy, dilated fundus examination, corneal pachymetry, corneal topography, and general medical findings. Targeted testing through PRDM5 gene sequencing with copy number variation detection was conducted. RESULTS: The 3 siblings included a 12-year-old boy and 8- and 6-year-old sisters, all of whom presented with myopia, blue-tinted sclerae, thin corneas, and variable corneal scarring. All 3 affected children were found to be homozygous for the PRDM5 gene variant c.1117_1123delinsTTTAATGCTTACAAATGTTTG p.Asp373Phefs*57. Coding sequences of PRDM5 and ZNF469 genes were sequenced in their entirety, and this was the only pathologic variant present in this family. The youngest affected sister developed persistent hydrops with severely decreased vision and underwent penetrating keratoplasty. Histopathology revealed severe corneal thinning, diffuse absence of Bowman layer, and ruptured Descemet membrane scrolls. CONCLUSIONS: Three siblings with clinical signs of BCS, including corneal thinning, myopia, and blue sclerae, were found to have a novel PRDM5 gene pathologic variant. This pathologic variant has not been previously reported, although 1 downstream nonsense pathologic variant has been reported as pathogenic. The similar phenotypes in all affected patients support the pathogenicity of this variant. Surgical management of BCS presents unique challenges due to severe tissue fragility.

Opacification of hydrophilic intraocular lenses associated with vitrectomy and injection of intraocular gas.

OBJECTIVE: To report 11 cases of intraocular lens (IOL) opacification after pars plana vitrectomy (PPV) involving intravitreal gas injection. METHODS AND ANALYSIS: Eleven cases of hydrophilic IOLs that opacified following PPV with intravitreal gas injection are described. Eight IOLs were explanted and analysed by light microscopy and scanning electron microscopy. Staining with alizarin red and von Kossa stains, as well as energy dispersive X-ray spectroscopy (EDX) were performed. Three IOLs were not explanted. The surgeons attached the clinical data. RESULTS: The IOLs were hydrophilic acrylic produced by six manufacturers. Six patients underwent primarily phacoemulsification with IOL implantation. PPV with intravitreal gas injection was performed 3 months-6 years afterwards. The other five patients underwent combined phacoemulsification with IOL implantation and PPV with intravitreal gas injection. IOL opacification was recorded 1 month -6 years after PPV. In eight patients, the IOLs were explanted 1 month-9 years after opacification was noticed. In three patients, the opacified IOL was not explanted. IOLs had opacified mainly anteriorly at the pupillary entrance or capsulorhexis opening. Light microscopy demonstrated granular surface deposits on the IOLs that stained positive for calcium by alizarin red and von Kossa stains. EDX analysis of the deposits detected calcium and phosphorus. CONCLUSIONS: Hydrophilic acrylic IOLs can opacify due to calcium deposition after PPV and intravitreal gas injection and may require IOL explantation. A hydrophobic IOL may be preferred when a simultaneous phacoemulsification and vitrectomy with intravitreal gas is performed.

The kinetics of early T and B cell immune recovery after bone marrow transplantation in RAG-2-deficient SCID patients.

The kinetics of T and B cell immune recovery after bone marrow transplantation (BMT) is affected by many pre- and post-transplant factors. Because of the profoundly depleted baseline T and B cell immunity in recombination activating gene 2 (RAG-2)-deficient severe combined immunodeficiency (SCID) patients, some of these factors are eliminated, and the immune recovery after BMT can then be clearly assessed. This process was followed in ten SCID patients in parallel to their associated transplant-related complications. Early peripheral presence of T and B cells was observed in 8 and 4 patients, respectively. The latter correlated with pre-transplant conditioning therapy. Cells from these patients carried mainly signal joint DNA episomes, indicative of newly derived B and T cells. They were present before the normalization of the T cell receptor (TCR) and the B cell receptor (BCR) repertoire. Early presentation of the ordered TCR gene rearrangements after BMT occurred simultaneously, but this pattern was heterogeneous over time, suggesting different and individual thymic recovery processes. Our findings early after transplant could suggest the long-term patients' clinical outcome. Early peripheral presence of newly produced B and T lymphocytes from their production and maturation sites after BMT suggests donor stem cell origin rather than peripheral expansion, and is indicative of successful outcome. Peripheral detection of TCR excision circles and kappa-deleting recombination excision circles in RAG-2-deficient SCID post-BMT are early markers of T and B cell reconstitution, and can be used to monitor outcome and tailor specific therapy for patients undergoing BMT.