Anophthalmia generally refers to an absence of the globe while the eyelids, conjunctiva, and lacrimal glands remain. Microphthalmia is a heterogeneous group of malformations with reduction in the size of the eyeball that is anatomically intact with only axial length reduction (simple form), or can also include anterior segment dysgenesis (complex form). Both anophthalmia and microphthalmia can occur as isolated or syndromic and can be bilateral or unilateral. Anterior segment dysgenesis generally refers to a complex spectrum of anomalies such as Axenfeld-Rieger anomaly and Peters anomaly where axial length may not be severely compromised. Syndromic forms can include Fraser syndrome, microphthalmia with linear skin defects, and Manitoba oculotrichoanal syndrome (MOTA).
This test is indicated for:
- Confirmation of a clinical diagnosis of anophthalmia, microphthalmia, or anterior segment dysgenesis/anomaly.
- Carrier testing in adults with a family history of anophthalmia, microphthalmia, or anterior segment dysgenesis/anomaly.
Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient's genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not meant to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient's gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.
Copy Number Analysis: Comparative analysis of the NGS read depth (coverage) of the targeted regions of genes on this panel was performed to detect copy number variants (CNV). The accuracy of the detected variants is highly dependent on the size of the event, the sequence context and the coverage obtained for the targeted region. Due to these variables and limitations a minimum validated CNV size cannot be determined; however, single exon deletions and duplications are expected to be below the detection limit of this analysis.
Clinical Sensitivity: Unknown. Pathogenic variants in the promoter region, some pathogenic variants in the introns and other regulatory element pathogenic variants cannot be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient's clinical and/or biochemical phenotype.
Analytical sensitivity for sequence variant detection is ~99%.
Copy Number Analysis: The sensitivity and specificity of this method for CNV detection is highly dependent on the size of the event, sequence context and depth of coverage for the region involved. The assay is highly sensitive for CNVs of 500 base pairs or larger and those containing at least 3 exons. Smaller (< 500 base pairs) CNVs and those that involving only 1 or 2 exons may or may not be detected depending on the sequence context, size of exon(s) involved and depth of coverage.
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Orangene™ Saliva Collection Kit used according to manufacturer instructions. Please contact EGL for a Saliva Collection Kit for patients that cannot provide a blood sample.
Please include fundus photographs, electroretinogram (ERG) findings, visual field findings, and visual acuity, if available, for expert review and clinical correlation with test results.
- Eye Disorders: Comprehensive Sequencing and Deletion/Duplication Panels
- Anophthalmia/Microphthalmia/Anterior Segment Dysgenesis/Anomaly: Deletion/Duplication Panel