Assessing non-Mendelian inheritance in inherited axonopathies

PURPOSE: Inherited axonopathies (IA) are rare, clinically and genetically heterogeneous diseases that lead to length-dependent degeneration of the long axons in central (hereditary spastic paraplegia [HSP]) and peripheral (Charcot–Marie–Tooth type 2 [CMT2]) nervous systems. Mendelian high-penetrance alleles in over 100 different genes have been shown to cause IA; however, about 50% of IA cases do not receive a genetic diagnosis. A more comprehensive spectrum of causative genes and alleles is warranted, including causative and risk alleles, as well as oligogenic multilocus inheritance. METHODS: Through international collaboration, IA exome studies are beginning to be sufficiently powered to perform a pilot rare variant burden analysis. After extensive quality control, our cohort contained 343 CMT cases, 515 HSP cases, and 935 non-neurological controls. We assessed the cumulative mutational burden across disease genes, explored the evidence for multilocus inheritance, and performed an exome-wide rare variant burden analysis. RESULTS: We replicated the previously described mutational burden in a much larger cohort of CMT cases, and observed the same effect in HSP cases. We identified a preliminary risk allele for CMT in the EXOC4 gene (p value= 6.9 × 10-6, odds ratio [OR] = 2.1) and explored the possibility of multilocus inheritance in IA. CONCLUSION: Our results support the continuing emergence of complex inheritance mechanisms in historically Mendelian disorders

Contactless eye-gaze tracking as a support for binocular vision impairments therapy

Na rynku znajduje się klika systemów pozwalających na badanie lub trening syndromu leniwego oka z użyciem komputera PC. Niewiele z nich bazuje na wirtualnej rzeczywistości. Większość jedynie skupia się na terapii niedowidzenia bez mierzenia jakichkolwiek parametrów lub wykonuje tylko same pomiary. Proponowane rozwiązanie to kompletny system diagnostyczno - terapeutyczny do detekcji i terapii zaburzeń widzenia obuocznego – zwłaszcza zeza (małego i średniego stopnia) oraz syndromu leniwego oka. Aby zapewnić większy obiektywizm badań prowadzonych przy użyciu opracowanego systemu, zastosowano śledzenie punktu fiksacji wzroku. System śledzenia punktu fiksacji charakteryzuje się brakiem jakichkolwiek fizycznych elementów montowanych na ciele użytkownika, zaś detekcja punktu fiksacji bazuje na analizie odbić promieni w zakresie podczerwieni.The lack of binocular vision is a serious vision impairment that deserves more attention. Binocular vision impairments often result in partial or total loss of stereoscopic vision. This paper describes a concept of a measurement and therapy system for the binocular vision impairments by using eye-gaze tracking system. The distance between human eyes and the LCD display is controlled by the gaze-tracking system. That system precisely analyzes the eye gazes and head position, and allows for taking measurements with a high precision. Because the measurement process is discrete, the interpolation and extrapolation algorithms of the results are required. When user looks on the screen between coordinates of the measurement points the new transform factors are calculated