A cataract is a loss of lens transparency. The crystalline lens plays a crucial role in the refractive vision by facilitating variable fine focusing of light onto the retina. Congenital cataracts are usually diagnosed at birth, failure to do so can result in permanent vision loss. They are the most common cause of visual impairment and blindness in children worldwide. Genetic, metabolic, traumatic and infectious factors can all lead to childhood cataracts. However, about one quarter of congenital cataracts are associated to genetic defects, are usually bilateral and quite heterogeneous. Congenital cataracts can be inherited in an autosomal dominant or recessive pattern as well as X-linked.
The Igenomix Congenital Cataracts Precision Panel can be used to make an accurate and directed diagnosis as well as a differential diagnosis of blindness ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
The clinical utility of this panel is:
GENE | OMIM DISEASES | INHERITANCE* | % GENE COVERAGE (20X) | HGMD** |
AGK | Congenital Cataract- | AR | 99.98 | 33 of 33 |
BCOR | Syndromic Micropthalmia, | X,XD,G | 99.87 | NA of NA |
BFSP1 | Cataract, Multiple | AD,AR | 97.54 | 7 of 8 |
BFSP2 | Autosomal Dominant | AD | 100 | 7 of 7 |
CAV1 | Lipodystrophy With | AD,AR | 100 | 18 of 18 |
CHMP4B | Cataract, Multiple | AD | 99.72 | 3 of 3 |
CRYAA | Cataract, Multiple | AD,AR | 100 | 26 of 26 |
CRYAB | Alpha-b Crystallinopathy, | AD,AR | 100 | 30 of 30 |
CRYBA1 | Congenital Zonular | AD | 100 | 14 of 14 |
CRYBA2 | Floriform | AD | 100 | 2 of 2 |
CRYBA4 | Cataract-Microcornea | AD | 100 | 11 of 11 |
CRYBB1 | Autosomal Recessive | AD,AR | 100 | 20 of 20 |
CRYBB2 | Congenital Cataract | AD | 100 | 28 of 28 |
CRYBB3 | Autosomal Recessive | AD,AR | 100 | 7 of 7 |
CRYGB | Cataract Multiple | AD | 99.57 | 2 of 2 |
CRYGC | Coppock-Like Cataract, | AD | 100 | 31 of 31 |
CRYGD | Crystalline Aculeiform | AD | 99.98 | 28 of 28 |
CRYGS | Membranous Cataract | AD | 100 | 9 of 9 |
CTDP1 | Congenital Cataracts, | AR | 97.52 | 0 of 1 |
EPHA2 | Posterior Polar Cataract, | AD | 100 | 24 of 24 |
EYA1 | Branchiootic Syndrome, | AD | 100 | 197 of 199 |
FAM126A | Hypomyelination And | AR | 100 | 11 of 12 |
FOXC1 | Axenfeld-Rieger Syndrome | AD | 88.98 | 94 of 100 |
FOXE3 | Familial Thoracic Aortic | AD,AR | 81.19 | 25 of 31 |
FTL | Hyperferritinemia- | AD,AR | 100 | 21 of 63 |
FYCO1 | Autosomal Recessive | AR | 99.98 | 20 of 20 |
GALK1 | Galactokinase | AR | 97.92 | 45 of 45 |
GCNT2 | Cataract With Adult | AD,AR | 97.19 | 9 of 10 |
GFER | Mitochondrial Progressive | AR | 99.89 | 6 of 6 |
GJA3 | Zonular Pulverulent | AD | 95.63 | 35 of 45 |
GJA8 | Zonular Pulverulent | AD | 99.2 | 72 of 73 |
HSF4 | Lamellar Cataract | AD | 100 | 26 of 26 |
IARS2 | Cataracts, Growth | AR | 99.95 | 11 of 11 |
INPP5K | Muscular Dystrophy, | AR | 92 | 10 of 10 |
LEMD2 | Cataract, Congenital Or | AR | 93.48 | 3 of 3 |
LIM2 | Cataract, Multiple | AR | 100 | 4 of 4 |
LSS | Alopecia-Mental Retardation | AR | 100 | 22 of 22 |
MAF | Ayme-Gripp Syndrome, | AD | 75.14 | 23 of 23 |
MED25 | Basel-Vanagaite–Smirin-Yosef | AR | 100 | 5 of 5 |
MIP | Cataract Multiple Types | AD | 100 | 29 of 29 |
MIR184 | Edict Syndrome | AD | na | na |
MIR204 | Retinal Dystrophy And | AD | na | na |
MSMO1 | Microcephaly, Congenital | AR | 99.78 | 4 of 4 |
NHS | Congenital Total Cataract | X,XD,G | 98.45 | NA of NA |
OCRL | Dent Disease, Lowe | X,XR,G | 100 | NA of NA |
P3H2 | Myopia, High, With | AR | 99.81 | NA of NA |
PANK4 | Neurodegeneration With | – | 99.6 | 1 of 1 |
PAX6 | Aniridia, Anterior Segment | AD | 100 | 460 of 485 |
PITX2 | Iridogoniodysgenesis Type 2, | AD | 99.97 | 104 of 107 |
PITX3 | Anterior Segment | AD,AR | 99.49 | 8 of 11 |
SIL1 | Marinesco-Sjogren | AR | 100 | 47 of 48 |
SIPA1L3 | Cataract | AR | 96.17 | 3 of 3 |
SLC16A12 | Juvenile Cataract, | AD | 99.95 | 18 of 18 |
SLC25A4 | Progressive External | AD,AR | 99.84 | 16 of 16 |
SLC33A1 | Congenital Cataracts, | AD,AR | 99.44 | 9 of 9 |
TDRD7 | Cataract, Autosomal | AR | 99.98 | 6 of 6 |
TKFC | Congenital | AR | 99.91 | NA of NA |
UNC45B | Cataract | AD | 99.72 | 6 of 6 |
VIM | Cataract Multiple | AD | 100 | 4 of 4 |
VSX2 | Microphthalmia With | AR | 100 | 13 of 13 |
WFS1 | Nuclear Total | AD,AR | 99.97 | 390 of 395 |
* Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial
** HGMD: Number of clinically relevant mutations according to HGMD
Shiels, A., & Hejtmancik, J. F. (2017). Mutations and mechanisms in congenital and age-related cataracts. Experimental eye research, 156, 95–102. https://doi.org/10.1016/j.exer.2016.06.011
Li, J., Chen, X., Yan, Y., & Yao, K. (2020). Molecular genetics of congenital cataracts. Experimental eye research, 191, 107872. https://doi.org/10.1016/j.exer.2019.107872
Shiels, A., & Hejtmancik, J. F. (2019). Biology of Inherited Cataracts and Opportunities for Treatment. Annual review of vision science, 5, 123–149. https://doi.org/10.1146/annurev-vision-091517-034346
Ceyhan, D., Schnall, B. M., Breckenridge, A., Fontanarosa, J., Lehman, S. S., & Calhoun, J. C. (2005). Risk factors for amblyopia in congenital anterior lens opacities. Journal of American Association for Pediatric Ophthalmology and Strabismus, 9(6), 537-541. doi:10.1016/j.jaapos.2005.09.001
Cassidy, L., & Taylor, D. (1999). Congenital cataract and multisystem disorders. Eye, 13(3), 464-473. doi:10.1038/eye.1999.123
Ma, A. S., Grigg, J. R., Ho, G., Prokudin, I., Farnsworth, E., Holman, K., Cheng, A., Billson, F. A., Martin, F., Fraser, C., Mowat, D., Smith, J., Christodoulou, J., Flaherty, M., Bennetts, B., & Jamieson, R. V. (2016). Sporadic and Familial Congenital Cataracts: Mutational Spectrum and New Diagnoses Using Next-Generation Sequencing. Human mutation, 37(4), 371–384. https://doi.org/10.1002/humu.22948
