The use of autozygosity mapping and next-generation sequencing in understanding anterior segment defects caused by an abnormal development of the lens.

摘要

The formation of the anterior segment of the eye is an intricate process that is dependent to a large degree on the normal development of the lens. Despite intensive study of the role of well-described eye genes, many causes of lenticular and anterior segment anomalies remain elusive. The majority of genes implicated thus far act in an autosomal dominant manner. Autosomal recessive causes are less well described; their diagnosis has been hindered by technological limitations, extreme genetic heterogeneity, a lack of understanding of eye biology and the role of many genes within the genome. The opportunity for the discovery of extremely rare autosomal recessive causes of ocular abnormalities from the study of consanguineous families is large, particularly through the powerful combination of next-generation sequencing with autozygosity mapping. Having begun to overcome the genetic heterogeneity bottleneck, it is increasingly recognised that the interpretation of genetic variants and the association of novel genes with a particular phenotype remain challenging. Nonetheless, increasing understanding of the genetic and mutational basis of lens and anterior segment abnormalities will be of enormous value to our comprehension of eye disease(s). Further, it will improve our ability to accurately interpret putative disease-causing variants with the aim of providing more personalised patient care and avoiding lifelong visual loss in children.