Novel variants in CDH2 are associated with a new syndrome including Peters anomaly. Clin Genet 2020 Mar;97(3):502-508
Date
10/28/2019Pubmed ID
31650526Pubmed Central ID
PMC7028510DOI
10.1111/cge.13660Scopus ID
2-s2.0-85074852685 (requires institutional sign-in at Scopus site) 13 CitationsAbstract
Peters anomaly (PA) is a congenital corneal opacity associated with corneo-lenticular attachments. PA can be isolated or part of a syndrome with most cases remaining genetically unsolved. Exome sequencing of a trio with syndromic PA and 145 additional unexplained probands with developmental ocular conditions identified a de novo splicing and three novel missense heterozygous CDH2 variants affecting the extracellular cadherin domains in four individuals with PA. Syndromic anomalies were seen in three individuals and included left-sided cardiac lesions, dysmorphic facial features, and decreasing height percentiles; brain magnetic resonance imaging identified agenesis of the corpus callosum and hypoplasia of the inferior cerebellar vermis. CDH2 encodes for N-cadherin, a transmembrane protein that mediates cell-cell adhesion in multiple tissues. Immunostaining in mouse embryonic eyes confirmed N-cadherin is present in the lens stalk at the time of separation from the future cornea and in the developing lens and corneal endothelium at later stages, supporting a possible role in PA. Previous studies in animal models have noted the importance of Cdh2/cdh2 in the development of the eye, heart, brain, and skeletal structures, also consistent with the patient features presented here. Examination of CDH2 in additional patients with PA is indicated to confirm this association.
Author List
Reis LM, Houssin NS, Zamora C, Abdul-Rahman O, Kalish JM, Zackai EH, Plageman TF Jr, Semina EVAuthor
Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Abnormalities, MultipleAnimals
Anterior Eye Segment
Antigens, CD
Cadherins
Child
Child, Preschool
Cornea
Corneal Opacity
Eye Abnormalities
Female
Genetic Predisposition to Disease
Heterozygote
Humans
Infant
Male
Mice
Mutation, Missense
