RESUMEN
BACKGROUND: Juvenile-onset primary open-angle glaucoma (JOAG), characterized by severe elevation of intraocular pressure and optic neuropathy prior to the age of 40, is a rare subtype of primary open-angle glaucoma. Several genetic mutations have been associated with JOAG. CASE SUMMARY: The proband patient was a young male, diagnosed with primary open-angle glaucoma at the age of 27. The patient and his unaffected parents who have been excluded from classic genetic mutations for primary open-angle glaucoma were included to explore for other possible genetic variants through whole genome sequencing and bioinformatics analysis. In this trio, we found two heterozygous variants inherited from the parents in the proband: c.281G>A, p.Arg94His in OLFM2 and c.177C>G, p.Ile59Met in SIX6. Both genetic mutations are predicted through bioinformatics analysis to replace evolutionary conserved amino acids, therefore rendering a pathogenic effect on proteins. In contrast, very low frequencies for these genetic mutations were recorded in most common control databases. CONCLUSION: This is the first report on coinherited mutations of OLFM2 and SIX6 in a JOAG family, which shows the complexity of JOAG inheritance. Large-scale clinical screening and molecular functional investigations on these coinherited mutations are imperative to improve our understanding of the development of JOAG.
RESUMEN
Purpose: Nanophthalmos is a rare genetic disorder commonly characterized by a short axial length (AL) and severe hyperopia. Mutations that have been identified through Mendelian genetic analysis can only explain a fraction of nanophthalmic cases. We investigate the clinically relevant genetic variants in nanophthalmos by whole-genome sequencing (WGS), including de novo mutations (DNMs) and inherited mutations. Methods: Clinically relevant genetic variants of 11 trios (11 nanophthalmic probands and their unaffected parents) from the Zhongshan Ophthalmic Center, China, were analyzed by WGS. We further screened three trios and 10 sporadic cases to identify the MYRF mutations. Results: In two of 11 trios, without evidence of the presence of deleterious inherited autosomal variants, two DNMs of MYRF (c.789delC, p.S264fs and c.789dupC, p.S264fs) were identified in the probands. These loss-of-function DNMs were predicted to result in premature stop codons and protein structure damage in both probands. In addition, deleterious inherited genetic variants in PRSS56 and MFRP were found in eight probands of the other nine trios. Expanded screening found an additional MYRF DNM (c.1433G>C, p.R478P) in one trio and a stop-gain MYRF mutation (c.2956C>T, p.R986X) in one sporadic case, suggesting the recurrence of MYRF mutations in nanophthalmic patients. Conclusions: This is the first trio-based WGS study for nanophthalmos, revealing the potential role of DNMs in MYRF and rare inherited genetic variants in PRSS56 and MFRP. The underlying mechanism of MYRF in the development of nanophthalmos needs to be further investigated.
Asunto(s)
Pueblo Asiatico/genética , Mutación del Sistema de Lectura , Proteínas de la Membrana/genética , Microftalmía/genética , Serina Proteasas/genética , Factores de Transcripción/genética , Adolescente , Adulto , Niño , China/epidemiología , Femenino , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Linaje , Análisis de Secuencia de ADN , Secuenciación Completa del GenomaRESUMEN
Point kernel integration (PKI) method is widely used in the visualization of radiation field in engineering applications because of the features of quickly dealing with large-scale complicated geometry space problems. But the traditional PKI programs have a lot of restrictions, such as complicated modeling, complicated source setting, 3D fine mesh results statistics and large-scale computing efficiency. To break the traditional restrictions for visualization of radiation field, ARShield was developed successfully. The results show that ARShield can deal with complicated plant radiation shielding problems for visualization of radiation field. Compared with SuperMC and QAD, it can be seen that the program is reliable and efficient. Also, ARShield can meet the demands of calculation speediness and interactive operations of modeling and displaying 3D geometries on a graphical user interface, avoiding error modeling in calculation and visualization.