Prevalence and related factors of myopic retinopathy - a hospital-based cross-section study in Vietnam.

CLINICAL RELEVANCE: Myopia prevention and anti-myopia treatment is of great importance in South East Asia. BACKGROUND: To evaluate the prevalence and related factors of myopic retinopathy in Vietnam. METHODS: A cross-sectional study was conducted on 168 eyes of 88 patients with high myopia presenting to the Refraction Department of Vietnam National Eye Hospital. Inclusion criteria were high myopia (≤-6.00D with cycloplegic retinoscopy). Consecutive presenting patients recruited between January 2020 and August 2020 consented to participate. RESULTS: Participant age range was 12-47 years. Peripapillary atrophy was present in 70.2% of participants, most commonly atrophy of one-quarter of the disc (38.7%). Central retinal changes were present in 66.1% of participants, subclassified as tessellated fundus in 60.7%, diffuse chorioretinal atrophy in 4.2% and patchy chorioretinal atrophy in 1.2%. Peripheral retinal lesions were present in 43.5% of participants, consisting of white-without-pressure in 32.1%, lattice degeneration in 16.1%, snail track degeneration in 4.2% and microcystoid degeneration in 1.2%. Myopia ≤-8.00D and axial length ≥26.5 mm were associated with additional risk of posterior ocular complications. Furthermore, age ≥19 years increased risk of central myopic retinopathy and ≥10 years since initial myopia diagnosis increased the risk of peripapillary atrophy and central retinal changes. Other factors such as the age of onset of myopia and family myopia history did not appear to alter the risk of peripheral retina damage. CONCLUSIONS: Retinal disorders were common in Vietnamese people with high myopia. Within the current cohort with high myopia, myopia ≤-8.00D and axial length ≥26.5 mm were associated with a significant further elevation of risk.

Novel mutations of the PAX6, FOXC1, and PITX2 genes cause abnormal development of the iris in Vietnamese individuals.

Purpose: Congenital iris abnormality is a feature of several genetic conditions, such as aniridia syndrome and anterior segment degeneration (ASD) disorders. Aniridia syndrome is caused by mutations in the PAX6 gene or its regulatory elements in the locus 11p13 or deletions of contiguous genes, while ASDs are the result of mutations in various genes, such as PAX6, FOXC1, PITX2, and CYP1B1. This study aims to identify pathogenic mutations in Vietnamese individuals with congenital anomalies of the iris. Methods: Genomic DNA was extracted from peripheral blood of 24 patients belonging to 15 unrelated families and their available family members. Multiplex ligation-dependent probe amplification (MLPA) was used to detect the deletions or duplications in the 11p13-14 region, including the PAX6 gene and its neighboring genes. Direct PCR sequencing was used to screen mutations in 13 exons and flanking sequences of the PAX6 gene. The patients without mutation in the PAX6 locus were further analyzed with whole exome sequencing (WES). Identified mutations were tested with segregation analysis in proband family members. Results: We identified a total of 8 novel and 4 recurrent mutations in 20 of 24 affected individuals from 12 families. Among these mutations, one large deletion of the whole PAX6 gene and another deletion of the PAX6 downstream region containing the DCDC1 and ELP4 genes were identified. Eight mutations were detected in PAX6, including four nonsense, three frameshift, and one splice site. In addition, two point mutations were identified in the FOXC1 and PITX2 genes in patients without mutation in PAX6. Some of the mutations segregated in an autosomal dominant pattern where family members were available. Conclusions: This study provides new data on causative mutations in individuals with abnormal development of iris tissue in Vietnam. These results contribute to clinical management and genetic counseling for affected people and their families.

Mutational screening of germline RB1 gene in Vietnamese patients with retinoblastoma reveals three novel mutations.

Purpose: Retinoblastoma (Rb) is a rare and unique eye cancer that usually develops in the retinas of children less than 5 years old due to mutations in the RB1 gene. About 40% of affected individuals have the heritable form making genetics testing of the RB1 gene important for disease management. This study aims to identify germline mutations in RB1 in a cohort of patients with Rb from northern Vietnam. Methods: Genomic DNA was extracted from peripheral blood of 34 patients with Rb (nine unilateral and 25 bilateral cases) and their available parents. Twenty-seven exons, flanking sequences, and the promoter region of RB1 gene were screened for mutations with direct PCR sequencing. Multiplex ligation-dependent probe amplification (MLPA) was applied for patients with negative sequencing results. In the mutation-positive patients, their available parental DNA was analyzed to determine the parental origin of the mutation. Results: Germline mutations in RB1 were identified in 25 (73.53%) of 34 patients (four unilateral and 21 bilateral cases). Of these mutations, 19 were detected, including seven nonsense, six frameshift, four splice-site (one was identified in two siblings), and one missense, with Sanger sequencing. Three novel frameshift mutations were discovered in one unilateral and two bilateral patients. MLPA detected mutations in the RB1 gene in six bilateral cases, of whom five had a whole gene deletion (three familial cases) and one had a partial gene deletion (from exon 4 to exon 27) in one allele of the RB1 gene. Parental testing showed five mutations originated from the fathers and one was inherited from a mother who was mosaic for the mutation. Conclusions: This study provides a data set of germline mutations in the RB1 gene in Vietnamese patients with retinoblastoma. Screening of mutations in the RB1 gene can help to identify heritable Rb and contribute to clinical management and genetic counseling for affected families.