Cataract 19 (CTRCT19) via the LIM2 Gene

Cataracts are defined 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. PubMed ID: 14743013). 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. PubMed ID: 8724637). LIM2-associated Cataract 19 (CTRCT19) is described as variable age of onset cortical pulverulent cataracts (Pras et al. 2002. PubMed ID: 11917274).

CTRCT19 is an autosomal recessive vision disorder that is caused by pathogenic sequence variants in the LIM2 gene, which encodes lens intrinsic membrane protein 2 (MP19) (Irum et al. 2016. PubMed ID: 27814360; Ponnam et al. 2008. PubMed ID: 18596884). MP19 is the second most abundant intrinsic membrane protein within the ocular lens and likely has a critical role in the development and/or maintenance of the ocular lens (Steele et al. 1997. PubMed ID: 9238094). Mouse mutant studies suggested that a homozygous missense variant in LIM2 (p.Cys51Arg) resulted in irregularly arranged lens fiber layers in the cortex. This variant in the heterozygous state resulted in reduced eye size, but visual properties were not affected. These results demonstrate that causative variants in this gene might have an effect on lens development in a semidominant manner (Puk et al. 2011. PubMed ID: 21617753).

To date, less than 5 pathogenic sequence variants have been reported, all of which are missense (Human Gene Mutation Database).

Due to the limited number of cases, predicting clinical sensitivity is difficult. All reported LIM2 pathogenic variants are detectable by sequencing.

This test provides full coverage of all coding exons of the LIM2 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).