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Invitae Congenital Cataracts Panel
Test description
The Invitae Congenital Cataracts Panel analyzes up to 38 genes that are associated with congenital cataracts, a condition characterized by lens opacity. These genes were curated based on the available evidence to date to provide a comprehensive analysis for inherited congenital cataracts. The genetic heterogeneity associated with congenital cataracts can make it difficult to use phenotype as the sole criterion to select a definitive cause. Comprehensive panel testing allows for an efficient evaluation of several potential genes based on a single clinical indication.
Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.
Genes tested
Primary panel
AGK BCOR BFSP1 BFSP2 CRYAA CRYAB CRYBA1 CRYBA4 CRYBB1 CRYBB2 CRYBB3 CRYGC CRYGD CRYGS CTDP1 EPHA2 FAM126A FOXC1 FYCO1 GALK1 GCNT2 GJA3 GJA8 HSF4 MAF MIP NHS OCRL PAX6 PITX2 PITX3 SIL1 TDRD7 VSX2
Add-on Preliminary-evidence Genes for Congenital Cataracts
CHMP4B CRYGB LIM2 VIM
Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.
Order test
Primary panel (34 genes)
Customized gene selection (0 included, 0 excluded)
AGK BCOR BFSP1 BFSP2 CRYAA CRYAB CRYBA1 CRYBA4 CRYBB1 CRYBB2 CRYBB3 CRYGC CRYGD CRYGS CTDP1 EPHA2 FAM126A FOXC1 FYCO1 GALK1 GCNT2 GJA3 GJA8 HSF4 MAF MIP NHS OCRL PAX6 PITX2 PITX3 SIL1 TDRD7 VSX2
Add-on Preliminary-evidence Genes for Congenital Cataracts (4 genes)
Customized gene selection (0 included, 0 excluded)
Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.
CHMP4B CRYGB LIM2 VIM
Clinical information
Disorders tested
- aniridia
- Axenfeld-Rieger syndrome
- Axenfeld-Rieger syndrome type 1
- Axenfeld-Rieger syndrome type 3
- Ayme-Gripp syndrome
- cataracts
- cataract types 1-6, 9-12, 14-18, 20-22, 33, 40
- cataract, syndromic 11
- cataract 13 with adult i phenotype
- cataract with late-onset corneal dystrophy
- congenital cataracts, facial dysmorphism, and neuropathy
- galactokinase deficiency with cataracts
- hypomyelination and congenital cataract type 5
- Dent disease 2
- foveal hypoplasia 1
- Gillespie syndrome
- iridogoniodysgenesis type 1
- iris hypoplasia and glaucoma
- keratitis
- Lowe syndrome
- Marinesco-Sjogren syndrome
- microphthalmia
- microphthalmia, syndromic 2
- microphthalmia with coloboma 3
- microphthalmia, isolated 2
- Nance-Horan syndrome
- optic nerve hypoplasia
- Peters anomaly
- Sengers syndrome
Clinical description
Bilateral congenital cataracts are the most common cause of treatable childhood blindness worldwide and are characterized by opacification of the lens. About 70% of individuals with congenital cataracts have abnormalities that are restricted to the lens, while 15% have additional eye findings and 15% have a multisystemic syndrome. Between a quarter and a third of congenital cataracts are believed to be hereditary, and a variety of environmental exposures are known to contribute to their development. The type of cataract is defined by its location in the lens (complete, polar/subcapsular, nuclear, lamellar, sutural, cortical, or membranous/capsular). Pathogenic genetic changes that cause cataracts are located within proteins that are important to maintain cell transparency and homeostasis. They are most commonly found within crystallins and connexins but can also occur in enzymes and in growth and transcription factors as well as in cytoskeletal, membranous, and cell-signaling proteins.
Clinical sensitivity
Based on the currently available publications, whose sample sizes are limited, the sensitivity of this panel is expected to be about 70% or greater for individuals with a clinical diagnosis of congenital cataracts.
Inheritance
Inherited cataracts can occur in several inheritance patterns, including autosomal dominant, autosomal recessive, and X-linked recessive.
Penetrance
Penetrance is generally high. Environmental factors can influence both the penetrance and the clinical heterogeneity of the disorder, particularly for cataracts that show onset after the congenital period.
Prevalence/Incidence
Bilateral congenital cataracts are the most common cause of treatable childhood blindness, with a prevalence of about 1–6 in 100,000 individuals in industrialized countries. In general, the prevalence of congenital cataracts is lower in industrialized countries than in the poorest regions of the world, where the prevalence is thought to range from 5–15 in 10,000 individuals.
References
- Churchill, A, Graw, J. Clinical and experimental advances in congenital and paediatric cataracts. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 2011; 366(1568):1234-49. PMID: 21402583
- Hejtmancik, JF. Congenital cataracts and their molecular genetics. Semin. Cell Dev. Biol. 2008; 19(2):134-49. PMID: 18035564
- Huang, B, He, W. Molecular characteristics of inherited congenital cataracts. Eur J Med Genet. 2010; 53(6):347-57. PMID: 20624502
- Deng, H, Yuan, L. Molecular genetics of congenital nuclear cataract. Eur J Med Genet. 2014; 57(2-3):113-22. PMID: 24384146
- Trumler, AA. Evaluation of pediatric cataracts and systemic disorders. Curr Opin Ophthalmol. 2011; 22(5):365-79. PMID: 21832913
- Santana, A, Waiswo, M. The genetic and molecular basis of congenital cataract. Arq Bras Oftalmol. 2011; 74(2):136-42. PMID: 21779674
- Guercio, JR, Martyn, LJ. Congenital malformations of the eye and orbit. Otolaryngol. Clin. North Am. 2007; 40(1):113-40, vii. PMID: 17346564
- Ma, AS, et al. Sporadic and Familial Congenital Cataracts: Mutational Spectrum and new Diagnoses using Next-Generation Sequencing. Hum. Mutat. 2015; :None. PMID: 26694549
Assay
Assay and technical information
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
| Gene | Transcript reference | Sequencing analysis | Deletion/Duplication analysis |
|---|---|---|---|
| AGK | NM_018238.3 | ||
| BCOR | NM_017745.5 | ||
| BFSP1 | NM_001195.4 | ||
| BFSP2 | NM_003571.3 | ||
| CHMP4B | NM_176812.4 | ||
| CRYAA | NM_000394.3 | ||
| CRYAB | NM_001885.2 | ||
| CRYBA1 | NM_005208.4 | ||
| CRYBA4 | NM_001886.2 | ||
| CRYBB1 | NM_001887.3 | ||
| CRYBB2 | NM_000496.2 | ||
| CRYBB3 | NM_004076.4 | ||
| CRYGB | NM_005210.3 | ||
| CRYGC | NM_020989.3 | ||
| CRYGD | NM_006891.3 | ||
| CRYGS | NM_017541.2 | ||
| CTDP1* | NM_004715.4 | ||
| EPHA2 | NM_004431.3 | ||
| FAM126A | NM_032581.3 | ||
| FOXC1 | NM_001453.2 | ||
| FYCO1 | NM_024513.3 | ||
| GALK1 | NM_000154.1 | ||
| GCNT2 | NM_001491.2 | ||
| GJA3 | NM_021954.3 | ||
| GJA8 | NM_005267.4 | ||
| HSF4 | NM_001538.3 | ||
| LIM2 | NM_030657.3 | ||
| MAF | NM_005360.4 | ||
| MIP | NM_012064.3 | ||
| NHS | NM_198270.3 | ||
| OCRL | NM_000276.3 | ||
| PAX6 | NM_000280.4 | ||
| PITX2 | NM_153427.2 | ||
| PITX3 | NM_005029.3 | ||
| SIL1 | NM_022464.4 | ||
| TDRD7 | NM_014290.2 | ||
| VIM | NM_003380.3 | ||
| VSX2 | NM_182894.2 |
CTDP1: Analysis is limited to the NM_004715.4:c.863+389C>T variant.
Resources
Patient resources
Patient guide: Genetic testing simplifiedReferences
- Churchill, A, Graw, J. Clinical and experimental advances in congenital and paediatric cataracts. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 2011; 366(1568):1234-49. PMID: 21402583
- Deng, H, Yuan, L. Molecular genetics of congenital nuclear cataract. Eur J Med Genet. 2014; 57(2-3):113-22. PMID: 24384146
- Guercio, JR, Martyn, LJ. Congenital malformations of the eye and orbit. Otolaryngol. Clin. North Am. 2007; 40(1):113-40, vii. PMID: 17346564
- Hejtmancik, JF. Congenital cataracts and their molecular genetics. Semin. Cell Dev. Biol. 2008; 19(2):134-49. PMID: 18035564
- Huang, B, He, W. Molecular characteristics of inherited congenital cataracts. Eur J Med Genet. 2010; 53(6):347-57. PMID: 20624502
- Ma, AS, et al. Sporadic and Familial Congenital Cataracts: Mutational Spectrum and new Diagnoses using Next-Generation Sequencing. Hum. Mutat. 2015; :None. PMID: 26694549
- Santana, A, Waiswo, M. The genetic and molecular basis of congenital cataract. Arq Bras Oftalmol. 2011; 74(2):136-42. PMID: 21779674
- Trumler, AA. Evaluation of pediatric cataracts and systemic disorders. Curr Opin Ophthalmol. 2011; 22(5):365-79. PMID: 21832913
