# Pathogenic Deep Intronic Variant in CNGB3 Identified From Whole-Genome Sequencing in an Unsolved Case of Patient Affected With Achromatopsia

## TL;DR

A 14-year-old patient with achromatopsia received a molecular diagnosis after a deep intronic variant in CNGB3 was identified through whole-genome sequencing.

## Contribution

The study identifies a novel pathogenic deep intronic variant in CNGB3 using whole-genome sequencing in an undiagnosed achromatopsia case.

## Key findings

- Whole-genome sequencing identified a second likely pathogenic CNGB3 variant in the patient.
- The molecular diagnosis enabled eligibility for gene therapy and vocational rehabilitation.
- The patient's 15-year diagnostic journey was resolved with this discovery.

## Abstract

Achromatopsia (ACHM) (MIM: 262300) is an autosomal recessive disorder characterized by reduced visual acuity and color blindness. In this report, we review the case of a 14-year-old male patient diagnosed with achromatopsia with a history of retinal dystrophy, cone dysfunction with normal dark-adapted response on ERG, congenital nystagmus, farsightedness, and astigmatism. The diagnostic exome sequencing previously revealed a single maternally inherited pathogenic CNGB3 variant (c.1148delC, p.(T383lfs∗13). Following enrollment in the Undiagnosed Rare Disease Clinic (URDC) at Indiana University School of Medicine (IUSM), genome sequencing (GS) identified a second CNGB3 known variant c.1663-1205G > A p.(Gly555Leufs∗33), which was classified as likely pathogenic. Identification of this variant in the patient provided the evidence needed for a molecular diagnosis and ended a 15-year diagnostic odyssey for the patient and his family. With a diagnosis, the patient is eligible for gene therapy and qualifies for the state-run Vocational Rehabilitation Program and bioptic driving.