Journal
CLINICAL GENETICS
Volume 86, Issue 5, Pages 475-481Publisher
WILEY
DOI: 10.1111/cge.12379
Keywords
COL4A1; microphthalmia; Peters anomaly; small vessel disease; stroke; whole exome sequencing
Categories
Funding
- National Institutes of Health by the Children's Hospital of Wisconsin [R01EY015518]
- Children's Hospital of Wisconsin
- Clinical and Translational Science Award (CTSA) program. [1UL1RR031973]
Ask authors/readers for more resources
Anophthalmia/microphthalmia (A/M) is a developmental ocular malformation defined as complete absence or reduction in size of the eye. A/M is a heterogenous disorder with numerous causative genes identified; however, about half the cases lack a molecular diagnosis. We undertook whole exome sequencing in an A/M family with two affected siblings, two unaffected siblings, and unaffected parents; the ocular phenotype was isolated with only mild developmental delay/learning difficulties reported and a normal brain magnetic resonance imaging (MRI) in the proband at 16months. No pathogenic mutations were identified in 71 known A/M genes. Further analysis identified a shared heterozygous mutation in COL4A1, c.2317G>A, p.(Gly773Arg) that was not seen in the unaffected parents and siblings. Analysis of 24 unrelated A/M exomes identified a novel c.2122G>A, p.(Gly708Arg) mutation in an additional patient with unilateral microphthalmia, bilateral microcornea and Peters anomaly; the mutation was absent in the unaffected mother and the unaffected father was not available. Mutations in COL4A1 have been linked to a spectrum of human disorders; the most consistent feature is cerebrovascular disease with variable ocular anomalies, kidney and muscle defects. This study expands the spectrum of COL4A1 phenotypes and indicates screening in patients with A/M regardless of MRI findings or presumed inheritance pattern.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available