Genetic landscape of isolated pediatric cataracts: extreme heterogeneity and variable inheritance patterns within genes. Hum Genet 2019 Sep;138(8-9):847-863
Date
09/07/2018Pubmed ID
30187164Pubmed Central ID
PMC6401332DOI
10.1007/s00439-018-1932-xScopus ID
2-s2.0-85052934727 (requires institutional sign-in at Scopus site) 48 CitationsAbstract
Pediatric cataract represents an important cause of pediatric visual impairment. While both genetic and environmental causes for pediatric cataract are known, a large proportion remains idiopathic. The purpose of this review is to discuss genes involved in isolated pediatric cataract, with a focus on variable inheritance patterns within genes. Mutations in over 52 genes are known to cause isolated pediatric cataract, with a major contribution from genes encoding for crystallins, transcription factors, membrane proteins, and cytoskeletal proteins. Interestingly, both dominant and recessive inheritance patterns have been reported for mutations in 13 different cataract genes. For some genes, dominant and recessive alleles represent distinct types of mutations, but for many, especially missense variants, there are no clear patterns to distinguish between dominant and recessive alleles. Further research into the functional effects of these mutations, as well as additional data on the frequency of the identified variants, is needed to clarify variant pathogenicity. Exome sequencing continues to be successful in identifying novel genes associated with congenital cataract but is hindered by the extreme genetic heterogeneity of this condition. The large number of idiopathic cases suggests that more genes and potentially novel mechanisms of gene disruption remain to be identified.
Author List
Reis LM, Semina EVAuthor
Elena V. Semina PhD Chief, Professor in the Ophthalmology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCataract
Child
Exome
Genetic Heterogeneity
Humans
Inheritance Patterns
Mutation
