Study of gene variants associated with retinopathy
Familial exudative vitreoretinopathy (FEVR) is a rare genetic disorder characterized by abnormal development of retinal blood vessels. The typical feature of the affected eye is an avascular area in the peripheral retina, which, depending on severity, can lead to vision-threatening complications. The eyeball lesions of FEVR are similar to retinopathy of prematurity, however most FEVR patients are born at term. To date, many genes have been identified with mutations causing FEVR, with inheritance patterns including: autosomal dominant/recessive inheritance and X-linked recessive inheritance. Defects in the Norrin/Frizzled4 signaling pathway are thought to be involved in FEVR disease. Fluorescein angiography is an important test in the diagnosis of FEVR, helping to detect the disease at an early stage and in asymptomatic family members.
The vitreous is responsible for keeping the center of the eye transparent so that light can reach the retina and let us begin to see.
To identify FEVR genetic mutations, commonly combined methods include gene sequencing to detect small gene mutations and molecular hybridization or gene amplification (PCR) to detect big changes in DNA. In this study, the team collected peripheral blood samples from pediatric patients diagnosed with FEVR at the National Eye Hospital in Hanoi, Vietnam, and their family members. All patients underwent a clinical ophthalmic examination, including ophthalmoscopy or fluorescein angiography.
Avascular retinal regions in patients with FEVR
Early diagnosis of FEVR and treatment are essential. In addition, family members of FEVR patients should also be encouraged to be screened. Therefore, genetic diagnosis plays an important role in determining the exact cause of the disease, and genetic counseling. Moreover, the research results of the topic also contribute to the database of polymorphisms of the gene causing FEVR in Vietnamese pediatric patients.
The process of sequencing and detecting disease-causing mutations
After the DNA of 20 pediatric patients was used for sequencing, new and rare variants were found in the FEVR-associated genes resulting in 11 pediatric patients identified as carrying or potentially pathogenic mutations causing disease, accounting for 55% of all pediatric patients. A total of 9 mutations were found in 4 genes causing FEVR, namely 3 heterozygous mutations in the FZD4 gene (3 patients), 3 semi-heterozygous mutations in the NDP gene (3 patients), 3 heterozygous mutations in the KIF11 gene (3 patients) and 1 homozygous variant in the ATOH7 gene (2 patients). Mutation types include 2 frameshift mutations, 7 nonsense mutations and 2 splicing mutations. In particular, 4 out of 11 mutations were new mutations and were not found in the control group of the 500 Vietnamese database.
Head and facial features of patient EVR-08 (A) carrying KIF11 mutation c.388-1G>C and patient EVR-11 (B) carrying KIF11 mutation c.2511_2515del. Both patients showed signs of microcephaly. Patient EVR-11 has atrophy of the eyeball in the left eye
The results obtained by the research team is the Dataset of variants of FEVR disease samples in Vietnam: A total of 12 pathogenic/potentially pathogenic mutations on genes causing the FEVR phenotype have been identified. In which, there are 4 new mutations that are not yet in the database of pathogenic mutations. The team's findings will provide useful information for the clinical management and genetic counseling of these pediatric patients, especially in asymptomatic cases, and contribute to the genetic counseling for families with a disease-causing mutation.The team looks forward to continuing to study a larger sample set, and use other methods to detect disease-causing mutations in patients with unknown causes.
Translated by Quoc Khanh
Link to Vietnamese version
