@article {2043, title = {Chorioretinal atrophy following voretigene neparvovec despite the presence of fundus autofluorescence.}, journal = {Mol Genet Genomic Med}, volume = {10}, year = {2022}, month = {2022 Nov}, pages = {e2038}, abstract = {

INTRODUCTION: Leber congenital amaurosis (LCA) type 2, due to disease-causing variants in RPE65, is characterized by severe visual loss in early infancy. Current treatments include voretigene neparvovec-rzyl (VN) for RPE65-associated LCA. Herein, we present the long-term follow-up of a patient treated with VN using quantitative autofluorescence (488\ nm excitation).

CASE REPORT: A 9-year-old girl with a diagnosis of LCA with biallelic variants in RPE65 presented for evaluation. The patient underwent VN treatment at the age of 11. The patient returned to clinic at age of 19 at which time imaging revealed evidence of chorioretinal atrophy. Quantitative autofluorescence performed prior to gene therapy and at 6- and 8-year follow-up revealed a central area of fundus autofluorescence.

DISCUSSION: This case report demonstrates acquisition of fundus autofluorescence at 6- and 8-year follow-up despite the development of chorioretinal atrophy.

}, keywords = {Atrophy, Child, cis-trans-Isomerases, Female, Humans, Leber Congenital Amaurosis, Mutation, Retinal Degeneration}, issn = {2324-9269}, doi = {10.1002/mgg3.2038}, author = {Kolesnikova, Masha and Lima de Carvalho, Jose Ronaldo and Parmann, Rait and Kim, Angela H and Mahajan, Vinit B and Tsang, Stephen H and Sparrow, Janet R} } @article {2021, title = {REPRODUCTIVE OPHTHALMOLOGY: The Intersection of Inherited Eye Diseases and Reproductive Technologies.}, journal = {Retina}, volume = {42}, year = {2022}, month = {2022 11 01}, pages = {2025-2030}, abstract = {

PURPOSE: To propose a working framework for patients with inherited eye diseases presenting to ophthalmologists who are interested in assisted reproductive technology and preimplantation genetic testing.

METHODS: Retrospective chart review and case series of three families with inherited eye diseases who successfully underwent preimplantation genetic testing, in vitro fertilization, and birth of unaffected children.

RESULTS: Preimplantation genetic testing was performed for three families with different inherited eye diseases, which included autosomal dominant retinitis pigmentosa, autosomal recessive achromatopsia, and X-linked Goltz syndrome. Preimplantation genetic testing led to the identification of unaffected embryos, which were then selected for in vitro fertilization and resulted in the birth of unaffected children.

CONCLUSION: A close collaboration between patients, families, ophthalmologists, reproductive genetic counselors, and reproductive endocrinology and infertility specialists is the ideal model for taking care of patients interested in preimplantation genetic testing for preventing the transmission of inherited eye diseases.

}, keywords = {Child, Eye Diseases, Hereditary, Female, Fertilization in Vitro, Humans, Ophthalmology, Pregnancy, Preimplantation Diagnosis, Retrospective Studies}, issn = {1539-2864}, doi = {10.1097/IAE.0000000000003591}, author = {Park, Jong G and Xu, Christine L and Boyd, Allison and Aghajanova, Lusine and Mahajan, Vinit B and Wood, Edward H} } @article {635, title = {Recessive coding and regulatory mutations in FBLIM1 underlie the pathogenesis of chronic recurrent multifocal osteomyelitis (CRMO).}, journal = {PLoS One}, volume = {12}, year = {2017}, month = {2017}, pages = {e0169687}, abstract = {

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, pediatric, autoinflammatory disease characterized by bone pain due to sterile osteomyelitis, and is often accompanied by psoriasis or inflammatory bowel disease. There are two syndromic forms of CRMO, Majeed syndrome and DIRA, for which the genetic cause is known. However, for the majority of cases of CRMO, the genetic basis is unknown. Via whole-exome sequencing, we detected a homozygous mutation in the filamin-binding domain of FBLIM1 in an affected child with consanguineous parents. Microarray analysis of bone marrow macrophages from the CRMO murine model (cmo) determined that the Fblim1 ortholog is the most differentially expressed gene, downregulated over 20-fold in the cmo mouse. We sequenced FBLIM1 in 96 CRMO subjects and found a second proband with a novel frameshift mutation in exon 6 and a rare regulatory variant. In SaOS2 cells, overexpressing the regulatory mutation showed the flanking region acts as an enhancer, and the mutation ablates enhancer activity. Our data implicate FBLIM1 in the pathogenesis of sterile bone inflammation and our findings suggest CRMO is a disorder of chronic inflammation and imbalanced bone remodeling.

}, keywords = {Amino Acid Sequence, Animals, Cell Adhesion Molecules, Cell Line, Tumor, Child, Cytoskeletal Proteins, Female, Genes, Recessive, Humans, Interleukin-10, Mice, Mutation, Osteomyelitis, Promoter Regions, Genetic, Sequence Homology, Amino Acid}, issn = {1932-6203}, doi = {10.1371/journal.pone.0169687}, author = {Cox, Allison J and Darbro, Benjamin W and Laxer, Ronald M and Velez, Gabriel and Bing, Xinyu and Finer, Alexis L and Erives, Albert and Mahajan, Vinit B and Bassuk, Alexander G and Ferguson, Polly J} } @article {671, title = {Autism Linked to Increased Oncogene Mutations but Decreased Cancer Rate.}, journal = {PLoS One}, volume = {11}, year = {2016}, month = {2016}, pages = {e0149041}, abstract = {

Autism spectrum disorder (ASD) is one phenotypic aspect of many monogenic, hereditary cancer syndromes. Pleiotropic effects of cancer genes on the autism phenotype could lead to repurposing of oncology medications to treat this increasingly prevalent neurodevelopmental condition for which there is currently no treatment. To explore this hypothesis we sought to discover whether autistic patients more often have rare coding, single-nucleotide variants within tumor suppressor and oncogenes and whether autistic patients are more often diagnosed with neoplasms. Exome-sequencing data from the ARRA Autism Sequencing Collaboration was compared to that of a control cohort from the Exome Variant Server database revealing that rare, coding variants within oncogenes were enriched for in the ARRA ASD cohort (p<1.0 x 10(-8)). In contrast, variants were not significantly enriched in tumor suppressor genes. Phenotypically, children and adults with ASD exhibited a protective effect against cancer, with a frequency of 1.3\% vs. 3.9\% (p<0.001), but the protective effect decreased with age. The odds ratio of neoplasm for those with ASD relative to controls was 0.06 (95\% CI: 0.02, 0.19; p<0.0001) in the 0 to 14 age group; 0.35 (95\% CI: 0.14, 0.87; p = 0.024) in the 15 to 29 age group; 0.41 (95\% CI: 0.15, 1.17; p = 0.095) in the 30 to 54 age group; and 0.49 (95\% CI: 0.14, 1.74; p = 0.267) in those 55 and older. Both males and females demonstrated the protective effect. These findings suggest that defects in cellular proliferation, and potentially senescence, might influence both autism and neoplasm, and already approved drugs targeting oncogenic pathways might also have therapeutic value for treating autism.

}, keywords = {Adolescent, Adult, Autism Spectrum Disorder, Child, Child, Preschool, Female, Genes, Tumor Suppressor, Genetic Predisposition to Disease, Humans, Infant, Male, Middle Aged, Mutation, Neoplasms, Oncogenes, Prevalence, Young Adult}, issn = {1932-6203}, doi = {10.1371/journal.pone.0149041}, author = {Darbro, Benjamin W and Singh, Rohini and Zimmerman, M Bridget and Mahajan, Vinit B and Bassuk, Alexander G} } @article {647, title = {Management of Pediatric Aphakic Glaucoma With Vitrectomy and Tube Shunts.}, journal = {J Pediatr Ophthalmol Strabismus}, volume = {53}, year = {2016}, month = {2016 Nov 01}, pages = {339-343}, abstract = {

PURPOSE: To review the impact of vitrectomy and tube shunts on mean intraocular pressure (IOP) and number of glaucoma medications in pediatric aphakic glaucoma.

METHODS: A retrospective review of pediatric patients who underwent combined vitrectomy and glaucoma tube shunt surgery for aphakic glaucoma was conducted. Inclusion criteria were: age 18 years or younger, diagnosis of aphakic glaucoma, preoperative IOP data, and postoperative IOP data for at least 6 months. Mean IOP lowering at 1 year, number of glaucoma medications at 1 year, and surgical complications, including tube occlusion in the postoperative period, were noted.

RESULTS: The mean \± standard deviation preoperative IOP was 33.9 \± 10.6 mm Hg (range: 18 to 57 mm Hg) with a mean of three topical IOP-lowering medications. A total of 5 (36\%) Ahmed and 9 (64\%) Baerveldt tube shunts were placed. One of the Baerveldt tube shunt procedures was combined with revision of a traumatically dislocated tube. The mean IOP at 12 months postoperatively was 16.6 \± 5.8 mm Hg (range: 6 to 28 mm Hg; P \< .01, t = 3.74, df = 13) with a mean of 2.3 glaucoma medications. There were no cases of tube occlusion, corneal decompensation, endophthalmitis, or retinal detachment over the 12 months of follow-up.

CONCLUSIONS: Combined vitrectomy and placement of a glaucoma tube shunt can be safe and effective in lowering IOP based on mean IOP values and number of glaucoma medications at 1 year. [J Pediatr Ophthalmol Strabismus. 2016;53(6):339-343.].

}, keywords = {Adolescent, Aphakia, Postcataract, Cataract, Cataract Extraction, Child, Child, Preschool, Female, Glaucoma, Glaucoma Drainage Implants, Humans, Infant, Intraocular Pressure, Male, Retrospective Studies, Visual Acuity, Vitrectomy}, issn = {1938-2405}, doi = {10.3928/01913913-20160818-01}, author = {Elshatory, Yasser M and Gauger, Elizabeth H and Kwon, Young H and Alward, Wallace L M and Boldt, H Culver and Russell, Stephen R and Mahajan, Vinit B} } @article {113, title = {23-gauge pediatric vitrectomy using limbus-based trocar-cannulas.}, journal = {Retina (Philadelphia, Pa.)}, volume = {32}, year = {2012}, month = {2012 May}, pages = {1023-7}, keywords = {Catheters, Child, Child, Preschool, Female, Glaucoma Drainage Implants, Humans, Infant, Male, Microsurgery, Retinal Detachment, Retrospective Studies, Vitrectomy, Vitreous Hemorrhage}, author = {Kay, Christine N and Quiram, Polly H and Mahajan, Vinit B} } @article {775, title = {Infrared imaging and optical coherence tomography reveal early-stage astrocytic hamartomas not detectable by fundoscopy.}, journal = {Am J Ophthalmol}, volume = {153}, year = {2012}, month = {2012 May}, pages = {883-889.e2}, abstract = {

PURPOSE: To describe and correlate the features of astrocytic hamartomas using multimodal imaging.

DESIGN: Prospective, noncomparative, observational case series.

METHODS: This was a single-center study of 4 patients (8 eyes) with tuberous sclerosis complex. A complete ophthalmologic examination, fundus photography, fundus autofluorescence (FAF), infrared imaging, and spectral-domain optical coherence tomography (SD-OCT) were performed for each patient. Images from each modality were analyzed and compared.

RESULTS: In 2 patients, infrared imaging and SD-OCT detected occult retinal astrocytic hamartomas that were not observed on clinical examination or color fundus photography. FAF demonstrated the greatest contrast between lesions and surrounding retina but failed to identify 1 occult lesion that was detected with infrared imaging and SD-OCT. SD-OCT revealed lesions arising from the retinal nerve fiber layer with overlying vitreous adhesions, hyperreflective dots, and optically empty spaces at all depths of the tumor. Hamartomas were hyporeflective on infrared imaging and hypoautofluorescent on FAF. FAF of some lesions demonstrated hyperautofluorescent spots.

CONCLUSIONS: Infrared imaging and SD-OCT aid in the detection of astrocytic hamartomas that are not visible on clinical examination or color fundus photography. SD-OCT enhances visualization of structural details. FAF is a useful adjunctive test to obtain greater contrast between lesions and surrounding retina. The ability to monitor structural changes over time in astrocytic hamartomas using SD-OCT may be beneficial for monitoring the success of systemic chemotherapy in the treatment of various tuberous sclerosis tumors.

}, keywords = {Adolescent, Astrocytes, Child, Diagnostic Imaging, Female, Fluorescein Angiography, Humans, Infrared Rays, Male, Ophthalmoscopes, Prospective Studies, Retinal Neoplasms, Tomography, Optical Coherence, Tuberous Sclerosis}, issn = {1879-1891}, doi = {10.1016/j.ajo.2011.10.033}, author = {Xu, Luna and Burke, Tomas R and Greenberg, Jonathan P and Mahajan, Vinit B and Tsang, Stephen H} } @article {157, title = {Collagen XVIII mutation in Knobloch syndrome with acute lymphoblastic leukemia.}, journal = {American journal of medical genetics. Part A}, volume = {152A}, year = {2010}, month = {2010 Nov}, pages = {2875-9}, abstract = {

Knobloch syndrome (KNO) is caused by mutations in the collagen XVIII gene (COL18A1) and patients develop encephalocele and vitreoretinal degeneration. Here, we report an El Salvadorian family where two sisters showed features of KNO. One of the siblings also developed acute lymphoblastic leukemia. DNA sequencing of COL18A1 revealed a homozygous, 2-bp deletion (c3514-3515delCT) in exon 41, which leads to abnormal collagen XVIII and deficiency of its proteolytic cleavage product endostatin. KNO patients with mutations in COL18A1 may be at risk for endostatin-related conditions including malignancy.

}, keywords = {Base Sequence, Child, Child, Preschool, Collagen Type XVIII, DNA Mutational Analysis, Encephalocele, Eye Abnormalities, Family, Female, Humans, Infant, Magnetic Resonance Imaging, Male, Molecular Sequence Data, Mutation, Pedigree, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Retinal Detachment}, author = {Mahajan, Vinit B and Olney, Ann Haskins and Garrett, Penny and Chary, Ajit and Dragan, Ecaterina and Lerner, Gary and Murray, Jeffrey and Bassuk, Alexander G} } @article {173, title = {A new macular dystrophy with anomalous vascular development, pigment spots, cystic spaces, and neovascularization.}, journal = {Archives of ophthalmology}, volume = {127}, year = {2009}, month = {2009 Nov}, pages = {1449-57}, abstract = {

To clinically phenotype an inherited macular dystrophy with peculiar intraretinal pigment spots, cysts, and hemorrhage in a 24-year-old female proband and her family.

}, keywords = {Adolescent, Adult, Amblyopia, Child, Child, Preschool, Cysts, Electroretinography, Female, Fluorescein Angiography, Humans, Macular Degeneration, Male, Middle Aged, Pedigree, Phenotype, Retinal Hemorrhage, Retinal Neovascularization, Retinal Pigment Epithelium, Retinal Vessels, Strabismus, Tomography, Optical Coherence, Visual Acuity, Young Adult}, author = {Mahajan, Vinit B and Russell, Stephen R and Stone, Edwin M} }