Cataract Type 39 via the CRYGB Gene

Cataracts are described as opacification of the crystalline lens of the eye that result in abnormal refraction index and light scattering. Congenital cataracts (CC) are a serious and leading cause of reversible blindness in childhood. They account for one-tenth of the cases of childhood blindness (Francis and Moore 2004). Estimated prevalence rate is 1.2 - 6.0 per 10,000 live births. Early diagnosis and surgery and optical correction have resulted in an improved outcome for infants with either unilateral or bilateral cataracts (Lambert and Drack 1996). CRYGB-associated cataracts has been described as three distinct phenotypes such as lamellar, anterior polar, and complete cataracts within the same family (Alfadhli et al. 2012).

Cataract Type 39 is an autosomal dominant disorder that is caused by pathogenic sequence variants in the crystallin, gamma-B (CRYGB) gene, which is located on chromosome 2q33-q37 (Alfadhli et al. 2012). The gamma-crystallin proteins play an important role in the maintenance of lens transparency and refractive index (Graw 1999). To date, two single nucleotide deletions have been reported in CRYGB gene (Human Gene Mutation Database; Alfadhli et al. 2012). 

Predicting clinical sensitivity for the CRYGB gene is difficult due to genetic heterogeneity. However, since only one pedigree containing CRYGB pathogenic variants has been reported so far (AlFadhli et al. 2012), variants in CRYGB are probably a relatively rare cause of cataracts.

This test provides full coverage of all coding exons of the CRYGB gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).