Whole-genome copy number variation analysis in anophthalmia and microphthalmia. Clin Genet 2013 Nov;84(5):473-81
Date
05/25/2013Pubmed ID
23701296Pubmed Central ID
PMC3985344DOI
10.1111/cge.12202Scopus ID
2-s2.0-84885863395 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
Anophthalmia/microphthalmia (A/M) represent severe developmental ocular malformations. Currently, mutations in known genes explain less than 40% of A/M cases. We performed whole-genome copy number variation analysis in 60 patients affected with isolated or syndromic A/M. Pathogenic deletions of 3q26 (SOX2) were identified in four independent patients with syndromic microphthalmia. Other variants of interest included regions with a known role in human disease (likely pathogenic) as well as novel rearrangements (uncertain significance). A 2.2-Mb duplication of 3q29 in a patient with non-syndromic anophthalmia and an 877-kb duplication of 11p13 (PAX6) and a 1.4-Mb deletion of 17q11.2 (NF1) in two independent probands with syndromic microphthalmia and other ocular defects were identified; while ocular anomalies have been previously associated with 3q29 duplications, PAX6 duplications, and NF1 mutations in some cases, the ocular phenotypes observed here are more severe than previously reported. Three novel regions of possible interest included a 2q14.2 duplication which cosegregated with microphthalmia/microcornea and congenital cataracts in one family, and 2q21 and 15q26 duplications in two additional cases; each of these regions contains genes that are active during vertebrate ocular development. Overall, this study identified causative copy number mutations and regions with a possible role in ocular disease in 17% of A/M cases.
Author List
Schilter KF, Reis LM, Schneider A, Bardakjian TM, Abdul-Rahman O, Kozel BA, Zimmerman HH, Broeckel U, Semina EVAuthors
Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of WisconsinKala Schilter in the CTSI department at Medical College of Wisconsin - CTSI
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
AdolescentAdult
Anophthalmos
Base Sequence
Child, Preschool
Chromosome Duplication
DNA Copy Number Variations
Eye Proteins
Female
Genome, Human
Homeodomain Proteins
Humans
Infant
Infant, Newborn
Male
Microphthalmos
Molecular Sequence Data
Neurofibromin 1
PAX6 Transcription Factor
Paired Box Transcription Factors
Phenotype
Repressor Proteins
SOXB1 Transcription Factors
Sequence Deletion
Severity of Illness Index
