Dominant variants in PRR12 result in unilateral or bilateral complex microphthalmia. Clin Genet 2021 Mar;99(3):437-442
Date
12/15/2020Pubmed ID
33314030Pubmed Central ID
PMC8259391DOI
10.1111/cge.13897Scopus ID
2-s2.0-85097633599 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
Complex microphthalmia is characterized by small eyes with additional abnormalities that may include anterior segment dysgenesis. While many genes are known, a genetic cause is identified in only 4-30% of microphthalmia, with the lowest rate in unilateral cases. We identified four novel pathogenic loss-of-function alleles in PRR12 in families affected by complex microphthalmia and/or Peters anomaly, including two de novo, the first dominantly transmitted allele, as well as the first splicing variant. The ocular phenotypes were isolated with no additional systemic features observed in two unrelated families. Remarkably, ocular phenotypes were asymmetric in all individuals and unilateral (with structurally normal contralateral eye) in three. There are only three previously reported PRR12 variants identified in probands with intellectual disability, neuropsychiatric disorders, and iris anomalies. While some overlap with previously reported cases is seen, nonsyndromic developmental ocular anomalies are a novel phenotype for this gene. Additional phenotypic expansions included short stature and normal development/cognition, each noted in two individuals in this cohort, as well as absence of neuropsychiatric disorders in all. This study identifies new associations for PRR12 disruption in humans and presents a genetic diagnosis resulting in unilateral ocular phenotypes in a significant proportion of cases.
Author List
Reis LM, Costakos D, Wheeler PG, Bardakjian T, Schneider A, Fung SSM, University of Washington Center for Mendelian Genomics, Semina EVAuthors
Deborah M. Costakos MD Chair, Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinElena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdolescentAdult
Alleles
Anterior Eye Segment
Child
Child, Preschool
Corneal Opacity
Eye Abnormalities
Female
Genetic Predisposition to Disease
Genetic Variation
Humans
Male
Membrane Proteins
Microphthalmos
Mutation
Pedigree
Phenotype
