Novel Mutation in CRYBB3 Causing Pediatric Cataract and Microphthalmia.

Up to 25% of pediatric cataract cases are inherited, with half of the known mutant genes belonging to the crystallin family. Within these, crystallin beta B3 (CRYBB3) has the smallest number of reported variants. Clinical ophthalmological and genetic-dysmorphological evaluation were performed in three autosomal dominant family members with pediatric cataract and microphthalmia, as well as one unaffected family member. Peripheral blood was collected from all participating family members and next-generation sequencing was performed. Bioinformatics analysis revealed a novel missense variant c.467G>A/p.Gly156Glu in CRYBB3 in all family members with childhood cataract. This variant is classified as likely pathogenic by ACMG, and no previous descriptions of it were found in ClinVar, HGMD or Cat-Map. The only other mutation previously described in the fifth exon of CRYBB3 is a missense variant that causes a change in amino acid from the same 156th amino acid to arginine and has been associated with pediatric cataract and microphthalmia. To the best of our knowledge, this is the first time the c.467G>A/p.Gly156Glu variant is reported and the second time a mutation in CRYBB3 has been associated with microphthalmia.

Overlapping Spectrum of Retinochoroidal Scarring in Congenital Zika Virus and Toxoplasmosis Infections.

BACKGROUND AND OBJECTIVE: Antenatal Zika virus (ZIKV) or toxoplasmosis infections may present with isolated eye abnormalities with absence of other apparent birth defects. The purpose of this article is to discuss the overlapping spectrum of clinical presentation and retinochoroidal scarring in congenital ZIKV and toxoplasmosis infections. PATIENTS AND METHODS: Prenatal ultrasound abnormalities seen from antenatal ZIKV and toxoplasmosis infections overlap and may include intracranial calcifications, microcephaly, and intrauterine growth restriction. The clinical spectrum of both infections in less severely affected infants and children may include nonspecific neurological impairment such as developmental delay and seizures. RESULTS: Inherent limitations in serological testing pose additional barriers in establishing a diagnosis. Retinal pigment epithelium (RPE) mottling in ZIKV infection can occur in isolation or adjacent to retinochoroidal atrophy. In contrast, RPE mottling outside of the borders of retinochoroidal atrophy is not typically seen in toxoplasmosis. To date, postnatal reactivation of congenital eye lesions as seen in toxoplasmosis have not been reported with ZIKV infection. CONCLUSIONS: As children infected with congenital ZIKV grow older, subclinical eye abnormalities may be indistinguishable from toxoplasmosis. Brazil has had high prevalence of both diseases with long-term information available on toxoplasmosis only. Surveillance guidelines for asymptomatic eye abnormalities will likely evolve. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:779-784.].