Identification of pathogenic variants for the development of ultra-long axial length in myopic children

TL;DR

This study identifies new genetic variants linked to extreme eye elongation in children with myopia, offering new insights for genetic screening.

Contribution

The study discovers five novel genetic variants and two distinct phenotypes associated with ultra-long axial length in myopic children.

Findings

Five novel genetic variants were identified in genes like BBS2, P4HA2, FBN1, LOXL3, and FZD4.

Two distinct phenotypes were observed in families F#5 and a non-syndromic child with BBS2.

The findings expand the genetic variant spectrum for myopia and suggest new screening targets.

Abstract

Axial elongation is a key factor in myopia progression, yet its genetic basis remains incompletely understood. This study aims to identify pathogenic genetic variants associated with excessively elongated axial length in children.

This study included 56 children with axial lengths exceeding the normal range for their age group, and whole-exome sequencing (WES) was performed on their oral mucosal samples. Clinical evaluations included axial length measurement, refraction testing, and fundus photography to assess the degree of myopia and retinal changes. Co-segregation analysis was conducted in selected families (F#1, F#2, F#5) to validate the familial inheritance patterns of the variants.

Fifteen children carried variants in genes including BBS2, OPN1LW, P4HA2, FBN1, LOXL3, FZD4, USH2A, COL2A1, and BFSP2, with five novel variants identified: BBS2 (c.700C > T), P4HA2 (c.1382C > G), FBN1 (c.7130T > C), LOXL3 (c.1580delC), and FZD4 (c.1315G > A). Notably, a rare compound heterozygous BBS2 variant (c.700C > T/c.534 + 1G > T) was found in a non-syndromic child, and the P4HA2 (c.419A > G) variant in family F#5 exhibited a phenotype distinct from previous studies.

This study identified five novel variants sites and discovered two cases with phenotypes distinct from previous studies, thereby expanding the genetic variant spectrum associated with myopia and providing new targets for genetic screening and intervention.

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