Clinical and mutation analysis of 51 probands with anophthalmia and/or severe microphthalmia from a single center. Issue 1 (27th March 2013)

• Record Type: Journal Article
• Authors: Gerth‐Kahlert, Christina; Williamson, Kathleen; Ansari, Morad; Rainger, Jacqueline K.; Hingst, Volker; Zimmermann, Theodor; Tech, Stefani; Guthoff, Rudolf F.; van, Veronica; FitzPatrick, David R.
• Is Part Of: Molecular genetics & genomic medicine. Volume 1:Issue 1(2013:May)
• Page Start: 15
• Page End: 31
• Publication Date: 2013-03-27
• Subjects: Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.2
• Languages: English
• ISSNs: 2324-9269

Abstract

<abstract abstract-type="main" xml:lang="en" id="brb32-abs-0001"> <title>Abstract</title> <p>Clinical evaluation and mutation analysis was performed in 51 consecutive probands with severe eye malformations – anophthalmia and/or severe microphthalmia – seen in a single specialist ophthalmology center. The mutation analysis consisted of bidirectional sequencing of the coding regions of <italic>SOX2</italic>, <italic>OTX2</italic>, <italic>PAX6</italic> (paired domain), <italic>STRA6</italic>, <italic>BMP4</italic>, <italic>SMOC1</italic>, <italic>FOXE3</italic>, and <italic>RAX</italic>, and genome‐wide array‐based copy number assessment. Fifteen (29.4%) of the 51 probands had likely causative mutations affecting <italic>SOX2</italic> (9/51), <italic>OTX2</italic> (5/51), and <italic>STRA6</italic> (1/51). Of the cases with bilateral anophthalmia, 9/12 (75%) were found to be mutation positive. Three of these mutations were large genomic deletions encompassing <italic>SOX2</italic> (one case) or <italic>OTX2</italic> (two cases). Familial inheritance of three intragenic, plausibly pathogenic, and heterozygous mutations was observed. An unaffected carrier parent of an affected child with an identified <italic>OTX2</italic> mutation confirmed the previously reported nonpenetrance for this disorder. Two families with <italic>SOX2</italic> mutations demonstrated a parent and child both with significant but highly variable eye malformations. Heterozygous loss‐of‐function mutations in <italic>SOX2</italic> and <italic>OTX2</italic> are the most common genetic pathology associated with severe eye malformations and bi‐allelic loss‐of‐function in <italic>STRA6</italic> is confirmed as an emerging cause of nonsyndromal eye malformations.</p> </abstract>