Faculty Collaboration Database

OTX2 microphthalmia syndrome: four novel mutations and delineation of a phenotype. Clin Genet 2011 Feb;79(2):158-68

Date

05/22/2010

Pubmed ID

20486942

Pubmed Central ID

PMC3017659

DOI

10.1111/j.1399-0004.2010.01450.x

Scopus ID

2-s2.0-78650917524 (requires institutional sign-in at Scopus site)   83 Citations

Abstract

The OTX2 homeobox-containing transcription factor gene was shown to play a key role in the development of head structures in vertebrates. In humans, OTX2 mutations result in anophthalmia/microphthalmia (A/M) often associated with systemic anomalies. We screened 52 unrelated individuals affected with A/M and identified disease-causing variants in four families (8%), a higher frequency than previously reported. All four mutations are predicted to result in truncation of normal OTX2 protein sequence, consistent with previously reported mechanisms; three changes occurred de novo and one mutation was inherited from an affected parent. Four of the five OTX2-positive patients in our study displayed additional systemic findings, including two novel features, Wolf-Parkinson-White syndrome and an anteriorly placed anus. Analysis of the phenotypic features of OTX2-positive A/M patients in this study and those previously reported suggests the presence of pituitary anomalies and lack of genitourinary and gastrointestinal manifestations as potential distinguishing characteristics from SOX2 anophthalmia syndrome. Interestingly, pituitary anomalies seem to be more strongly associated with mutations that occur in the second half of OTX2, after the homeodomain and SGQFTP motif. OTX2 patients also show a high rate of inherited mutations (35%), often from mildly or unaffected parents, emphasizing the importance of careful parental examination/testing.

Author List

Schilter KF, Schneider A, Bardakjian T, Soucy JF, Tyler RC, Reis LM, Semina EV

Authors

Kala 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

Anophthalmos
Child, Preschool
Female
Gene Deletion
Humans
Infant
Male
Microphthalmos
Mutation
Otx Transcription Factors
Pedigree
Phenotype
Syndrome