Journal article
Novel Intragenic PAX6 Deletion in a Pedigree with Aniridia, Morbid Obesity, and Diabetes
Current eye research, Vol.45(1), pp.91-96
01/02/2020
DOI: 10.1080/02713683.2019.1649704
PMID: 31361967
Abstract
Aniridia is a rare congenital eye disease, characterized by a constellation of symptoms including hypoplastic irides, foveal hypoplasia, early cataract, corneal stem cell deficiency, and glaucoma. Large chromosomal deletions spanning the PAX6 gene cause WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and intellectual disability [formerly called mental retardation]). We describe clinical and genetic studies of a three-generation pedigree with aniridia along with additional systemic conditions (morbid obesity, diabetes) suggesting the possibility of a contiguous-gene syndrome like WAGR.
Clinical records were obtained and DNA was prepared from blood samples from three of the four patients and tested for mutations in the coding sequences of the PAX6 gene. The index patient also had cardiomyopathy and was tested for known cardiomyopathy genetic mutations using a next-generation DNA sequencing assay.
We discovered a novel intragenic PAX6 mutation, a 16 bp heterozygous deletion c.203delCCAGGGCAATCGGTGG, with Sanger sequencing that is the likely cause of autosomal dominant aniridia in this pedigree. This PAX6 deletion causes a frameshift in predicted protein translation and a subsequent premature termination, p.Pro68Leufs*6. The PAX6 deletion was detected in all three available family members with aniridia, the index patient, his mother, and his maternal aunt but was not observed in the
Ex
ome
A
ggregation
C
onsortium (ExAC) database. Targeted sequencing of known cardiomyopathy genes in the index patient identified a second mutation, a 1.7 Mp deletion that spans the MYBPC3 gene.
We report a pedigree with aniridia and other systemic abnormalities that were initially suspicious for a contiguous-gene syndrome like WAGR. However, genetic analysis of the pedigree revealed two independent genetic abnormalities on chromosome 11p: 1) a novel PAX6 mutation, and 2) a large chromosome deletion spanning MYBPC3, a known cardiomyopathy gene. It is unclear if morbid obesity and type II diabetes mellitus have a related genetic cause.
Details
- Title: Subtitle
- Novel Intragenic PAX6 Deletion in a Pedigree with Aniridia, Morbid Obesity, and Diabetes
- Creators
- Erin A Boese - University of Iowa, Ophthalmology and Visual SciencesMallory R Tollefson - University of IowaMichael J Schnieders - University of Iowa, Roy J. Carver Department of Biomedical EngineeringBenjamin W Darbro - University of Iowa, Stead Family Department of PediatricsWallace L.M Alward - University of Iowa, Ophthalmology and Visual SciencesJohn H Fingert - University of Iowa, Ophthalmology and Visual Sciences
- Resource Type
- Journal article
- Publication Details
- Current eye research, Vol.45(1), pp.91-96
- DOI
- 10.1080/02713683.2019.1649704
- PMID
- 31361967
- NLM abbreviation
- Curr Eye Res
- ISSN
- 0271-3683
- eISSN
- 1460-2202
- Publisher
- Taylor & Francis
- Grant note
- name: Hadley-Carver Chair in Glaucoma, award: Not Applicable; DOI: 10.13039/100001818, name: Research to Prevent Blindness, award: Not Applicable
- Language
- English
- Date published
- 01/02/2020
- Academic Unit
- Medical Genetics and Genomics; Biochemistry and Molecular Biology; Ophthalmology and Visual Sciences
- Record Identifier
- 9984107836002771
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