Novel compound heterozygous mutations in ABCA4 in a Chinese pedigree with Stargardt disease.

PURPOSE: Stargardt disease (STGD) is a common macular dystrophy in juveniles that is commonly inherited as an autosomal recessive trait. Mutations in five genes (ABCA4, PROM1, ELOVL4, BEST1, and PRPH2) have been reported to be associated with STGD. In the present study, we aimed to identify the pathogenic mutations in affected members in a Chinese STGD pedigree. METHODS: One patient was selected for whole-exome sequencing. Variants in five candidate genes were identified initially, followed by several filtering steps against public and private variation databases (1000Genomes, ESP6500si, ExAC, and in-house database), as well as bioinformatic analysis of the putative pathogenic roles. Sanger sequencing was used for cosegregation analysis among all members with available DNA. RESULTS: Two mutations in ABCA4 (NM_000350.2; c.5646G>A; p.Met1882Ile and NM_000350.2; c.3523-2A>G) were found using whole-exome sequencing. Cosegregation analysis confirmed all the affected members carried the compound heterozygous mutations while the other healthy members had at most one. The missense mutation was extremely rare in public databases and predicted to be deleterious. The splice-site mutation was absent from all public and private databases and was predicted to alter the splice pattern, resulting in an exon skip and a frameshift. CONCLUSIONS: Using whole-exome sequencing, we found novel compound heterozygous mutations in ABCA4 in a Chinese STGD pedigree. These mutations are reported for the first time, therefore widening the mutation spectrum of Stargardt disease. The present study also illustrates the potential of whole-exome sequencing in determining the genetic cause of STGD.

Observation on the curative effect of horizontal rectus transposition combining recess-resect treatment on monocular elevation deficiency with horizontal strabismus.

Purpose: To explore the clinical effect of horizontal rectus transposition combining recess and resect treatment on monocular elevation deficiency (MED) with horizontal strabismus. Methods: Ten patients (10 eyes) scheduled to undergo horizontal rectus transposition combining recess-resect surgery to treat MED with horizontal strabismus in the ME Department of Ophthalmology of the First Affiliated Hospital of Guangxi Medical University between July 2016 and February 2022 were included in the study. The degree of vertical and horizontal prism strabismus, the grading of upper movement of the paralyzed eye, and the improvement of binocular vision were evaluated before and after the surgery. Results: Horizontal rectus transposition combined with recess and resect treatment was used to treat 10 patients with MED combined with horizontal strabismus. A good curative effect was seen in eight patients. The differences in the degree of vertical strabismus, the degree of horizontal strabismus, and the movement function of the paretic eyes before and after surgery were significantly different (all P < 0.05). The binocular haplopia function in six patients was reconstructed in the primary position after surgery. Conclusion: Horizontal rectus transposition combining recess-resect is easy to perform, and the number of recti involved in the surgery is small. This approach can effectively correct the eye position, improve eye movement, and reconstruct binocular vision in patients with MED by combining horizontal strabismus.

A novel NHS mutation in a Chinese family with Nance­Horan Syndrome.

Nance­Horan syndrome (NHS) is a rare X­linked disorder with various clinical manifestations. The present study aimed to identify the pathogenic mutation causing NHS in a three­generation Chinese family with 4 individuals presenting primarily with congenital cataracts. The genomic DNA of 5 individuals was collected, and family history and clinical information were recorded. Whole exome sequencing was performed on the proband, and candidate mutations were filtered by a series of screening processes and validated by Sanger sequencing. The identified pathogenic mutation was confirmed by co­segregation analysis. Finally, a novel frameshift mutation (NM_001291867.1: c.302dupA; p.Ala102fs) was identified in the NHS actin remodeling regulator (NHS) gene, which co­segregated with congenital cataracts in this family. Carrier females exhibited similar but milder clinical symptoms compared with the affected male. These clinical symptoms were consistent with the phenotypic features of the NHS­associated disease, NHS. In summary, the present study identified a novel NHS mutation in a Chinese family with atypical NHS; the results broaden the known pathogenic mutation spectrum of NHS and will aid in the genetic counseling of patients with NHS. The data from the present study also suggest that genetic analysis may be required for the diagnosis of this disease.

Fundus examination of 199 851 newborns by digital imaging in China: a multicentre cross-sectional study.

BACKGROUND: The prevalence of ocular abnormalities of newborn in China has seldom been reported. To report the implementation of digital imaging in ocular screening of all newborns in multiple centres in China and to describe the abnormal findings of fundus examination, we did the cross-sectional study. METHODS: Fundus examinations were performed on newborns within the 42 days after birth using a RetCam wide-field digital imaging system. Digital images of the posterior pole, superior, nasal and temporal retinal fields of each participant were taken. All newborns were from eights centres across China from January 2009 to July 2017. RESULTS: A total of 199 851 newborns were included in the study. We detected 18 198 (9.11%) abnormal cases. The most frequent abnormality was severe retinal haemorrhage (RH) found in 12 810 cases (6.41%). The other anomalies included familial exudative vitreoretinopathy, retinopathy of prematurity, abnormal fundus pigmentation, subconjunctival haemorrhage, choroidal coloboma, idiopathic retinal venous tortuosity, exudative changes and other anomalies with uncertain identities. CONCLUSION: This large-scale study of newborn fundus examination showed a relatively high prevalence of ocular abnormalities. Hundreds of neonates with rare disorders that severely impair ocular health were also detected at an early age. The long-term impact of other anomalies including RHs on the ocular system should be investigated by a perspective study. Our study suggested that fundus examination of newborns can play a beneficial role in ocular health.