Development and validation of a new vision screening test algorithm for public use mobile application- A pilot study

@#algorithm for mobile application and perform a pilot study todetermine its validity and reliability as a tool for vision testin the community.Methods: A simple visual acuity test algorithm in the form ofa single letter E display was designed as the optotype fordevelopment of a mobile application. The standardisedoptotype is presented at random to test visual acuity forcorresponding level of 3/60, 6/60, 6/18, and 6/12. The finalresult is auto-generated based on the classification of theWHO for visual impairment and blindness. The Snellen chartwas used as the gold standard to determine its validity whilefive different users were involved to determine its inter-raterreliability. A pilot study was performed between April tillNovember 2019, in the Universiti Sultan Zainal AbidinMedical Centre (UMC) at Kuala Nerus and MoorisOptometrist Centre at Marang, Terengganu. A total of 279participants aged four years old and above were involved inthis study. Results: The highest sensitivity was found at the vision levelcut-off point of 6/12 with the percentage of 92.7% and 86.8%for the right and left eye, respectively. The specificity wasmore than 89% for all vision levels in both eyes. TheKrippendorff’s alpha value for the inter-rater reliability was0.87 and 0.83.Conclusion: The relatively high level of validity andreliability obtained indicate the feasibility of using thedesigned optotype to develop a valid and reliable mobile appfor vision test. The app can be used to screen vision by non-medical persons, at anytime and anywhere to help improvepublic awareness and capability to correctly determine theirvisual status.

Screening of the LIX1 gene in Japanese and Malaysian patients with SMA and/or SMA-like disorder.

BACKGROUND: The majority of spinal muscular atrophy (SMA) patients showed homozygous deletion or other mutations of SMN1. However, the genetic etiology of a significant number of SMA patients has not been clarified. Recently, mutation in the gene underlying cat SMA, limb expression 1 (LIX1), has been reported. Similarity in clinical and pathological features of cat and human SMA may give an insight into possible similarity of the genetic etiology. PATIENTS AND METHODS: In this study, we screened for a mutation in LIX1 using direct DNA sequencing in our SMA and/or SMA-like patients who retained SMN1. A total of 33 patients were enrolled in this study, of which 22 were Japanese and 11 were Malaysians. All these patients possessed at least two copies of SMN1. RESULTS: We did not identify any pathogenic mutations in the coding regions or splice sites of LIX1 in the patients. In addition, we described a polymorphism within LIX1 intron 3, c.387+107A>T. We found that A-allele is significantly more frequent in SMA patients compared to normal individuals. CONCLUSION: Molecular genetic analysis of our SMA and/or SMA-like patients suggests that LIX1 is not associated with the development of their disorders. However, the number of patients analyzed in this study was very limited, and a larger study with bigger sample size is needed to confirm this result.

Combination of SMN2 copy number and NAIP deletion predicts disease severity in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations in the SMN1 gene. The SMN2 gene is highly homologous to SMN1 and has been reported to be correlated with severity of the disease. The clinical presentation of SMA varies from severe to mild, with three clinical subtypes (type I, type II, and type III) that are assigned according to age of onset and severity of the disease. Here, we aim to investigate the potential association between the number of copies of SMN2 and the deletion in the NAIP gene with the clinical severity of SMA in patients of Malaysian origin. Forty-two SMA patients (14 of type I, 20 type II, and 8 type III) carrying deletions of the SMN1 gene were enrolled in this study. SMN2 copy number was determined by fluorescence-based quantitative polymerase chain reaction assay. Twenty-nine percent of type I patients carried one copy of SMN2, while the remaining 71% carried two copies. Among the type II and type III SMA patients, 29% of cases carried two copies of the gene, while 71% carried three or four copies of SMN2. Deletion analysis of NAIP showed that 50% of type I SMA patients had a homozygous deletion of exon 5 of this gene and that only 10% of type II SMA cases carried a homozygous deletion, while all type III patients carried intact copies of the NAIP gene. We conclude that there exists a close relationship between SMN2 copy number and SMA disease severity, suggesting that the determination of SMN2 copy number may be a good predictor of SMA disease type. Furthermore, NAIP gene deletion was found to be associated with SMA severity. In conclusion, combining the analysis of deletion of NAIP with the assessment of SMN2 copy number increases the value of this tool in predicting the severity of SMA.