Faculty Collaboration Database

Whole exome sequence analysis of Peters anomaly. Hum Genet 2014 Dec;133(12):1497-511

Date

09/04/2014

Pubmed ID

25182519

Pubmed Central ID

PMC4395516

DOI

10.1007/s00439-014-1481-x

Scopus ID

2-s2.0-84920418405 (requires institutional sign-in at Scopus site)   53 Citations

Abstract

Peters anomaly is a rare form of anterior segment ocular dysgenesis, which can also be associated with additional systemic defects. At this time, the majority of cases of Peters anomaly lack a genetic diagnosis. We performed whole exome sequencing of 27 patients with syndromic or isolated Peters anomaly to search for pathogenic mutations in currently known ocular genes. Among the eight previously recognized Peters anomaly genes, we identified a de novo missense mutation in PAX6, c.155G>A, p.(Cys52Tyr), in one patient. Analysis of 691 additional genes currently associated with a different ocular phenotype identified a heterozygous splicing mutation c.1025+2T>A in TFAP2A, a de novo heterozygous nonsense mutation c.715C>T, p.(Gln239*) in HCCS, a hemizygous mutation c.385G>A, p.(Glu129Lys) in NDP, a hemizygous mutation c.3446C>T, p.(Pro1149Leu) in FLNA, and compound heterozygous mutations c.1422T>A, p.(Tyr474*) and c.2544G>A, p.(Met848Ile) in SLC4A11; all mutations, except for the FLNA and SLC4A11 c.2544G>A alleles, are novel. This is the first study to use whole exome sequencing to discern the genetic etiology of a large cohort of patients with syndromic or isolated Peters anomaly. We report five new genes associated with this condition and suggest screening of TFAP2A and FLNA in patients with Peters anomaly and relevant syndromic features and HCCS, NDP and SLC4A11 in patients with isolated Peters anomaly.

Author List

Weh E, Reis LM, Happ HC, Levin AV, Wheeler PG, David KL, Carney E, Angle B, Hauser N, Semina EV

Author

Elena 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

Amino Acid Sequence
Anion Transport Proteins
Anterior Eye Segment
Antiporters
Child
Corneal Opacity
DNA Mutational Analysis
Exome
Eye Abnormalities
Eye Proteins
Filamins
Genetic Association Studies
Genetic Predisposition to Disease
Homeodomain Proteins
Humans
Infant
Lyases
Male
Molecular Sequence Data
Mutation, Missense
Nerve Tissue Proteins
PAX6 Transcription Factor
Paired Box Transcription Factors
Pedigree
Prenatal Diagnosis
Repressor Proteins
Sequence Analysis, RNA
Transcription Factor AP-2