Whole-genome copy number variation analysis in anophthalmia and microphthalmia

Kf Schilter, Lm Reis, A. Schneider, Tm Bardakjian, O. Abdul-Rahman, Ba Kozel, Hh Zimmerman, U. Broeckel, Ev Semina

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)473-481
Number of pages9
JournalClinical Genetics
Volume84
Issue number5
DOIs
StatePublished - Nov 1 2013

Fingerprint

Anophthalmos
Microphthalmos
Genome
Mutation
Eye Diseases
Genes
Vertebrates
Phenotype

Keywords

  • 2q14
  • 3q29
  • Anophthalmia
  • Copy number variation
  • Microphthalmia
  • NF1
  • PAX6
  • SOX2

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Schilter, K., Reis, L., Schneider, A., Bardakjian, T., Abdul-Rahman, O., Kozel, B., ... Semina, E. (2013). Whole-genome copy number variation analysis in anophthalmia and microphthalmia. Clinical Genetics, 84(5), 473-481. https://doi.org/10.1111/cge.12202

Whole-genome copy number variation analysis in anophthalmia and microphthalmia. / Schilter, Kf; Reis, Lm; Schneider, A.; Bardakjian, Tm; Abdul-Rahman, O.; Kozel, Ba; Zimmerman, Hh; Broeckel, U.; Semina, Ev.

In: Clinical Genetics, Vol. 84, No. 5, 01.11.2013, p. 473-481.

Research output: Contribution to journalArticle

Schilter, K, Reis, L, Schneider, A, Bardakjian, T, Abdul-Rahman, O, Kozel, B, Zimmerman, H, Broeckel, U & Semina, E 2013, 'Whole-genome copy number variation analysis in anophthalmia and microphthalmia', Clinical Genetics, vol. 84, no. 5, pp. 473-481. https://doi.org/10.1111/cge.12202
Schilter K, Reis L, Schneider A, Bardakjian T, Abdul-Rahman O, Kozel B et al. Whole-genome copy number variation analysis in anophthalmia and microphthalmia. Clinical Genetics. 2013 Nov 1;84(5):473-481. https://doi.org/10.1111/cge.12202
Schilter, Kf ; Reis, Lm ; Schneider, A. ; Bardakjian, Tm ; Abdul-Rahman, O. ; Kozel, Ba ; Zimmerman, Hh ; Broeckel, U. ; Semina, Ev. / Whole-genome copy number variation analysis in anophthalmia and microphthalmia. In: Clinical Genetics. 2013 ; Vol. 84, No. 5. pp. 473-481.
@article{cf015c875394415185b78eac312d546d,
title = "Whole-genome copy number variation analysis in anophthalmia and microphthalmia",
abstract = "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.",
keywords = "2q14, 3q29, Anophthalmia, Copy number variation, Microphthalmia, NF1, PAX6, SOX2",
author = "Kf Schilter and Lm Reis and A. Schneider and Tm Bardakjian and O. Abdul-Rahman and Ba Kozel and Hh Zimmerman and U. Broeckel and Ev Semina",
year = "2013",
month = "11",
day = "1",
doi = "10.1111/cge.12202",
language = "English (US)",
volume = "84",
pages = "473--481",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Whole-genome copy number variation analysis in anophthalmia and microphthalmia

AU - Schilter, Kf

AU - Reis, Lm

AU - Schneider, A.

AU - Bardakjian, Tm

AU - Abdul-Rahman, O.

AU - Kozel, Ba

AU - Zimmerman, Hh

AU - Broeckel, U.

AU - Semina, Ev

PY - 2013/11/1

Y1 - 2013/11/1

N2 - 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.

AB - 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.

KW - 2q14

KW - 3q29

KW - Anophthalmia

KW - Copy number variation

KW - Microphthalmia

KW - NF1

KW - PAX6

KW - SOX2

UR - http://www.scopus.com/inward/record.url?scp=84885863395&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885863395&partnerID=8YFLogxK

U2 - 10.1111/cge.12202

DO - 10.1111/cge.12202

M3 - Article

C2 - 23701296

AN - SCOPUS:84885863395

VL - 84

SP - 473

EP - 481

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 5

ER -