Early Onset Horizontal Gaze Palsy and Progressive Scoliosis Due to a Noncanonical Splicing-Site Variant and a Missense Variant in the ROBO3 Gene

Authors

Sheng Yi
Zailong Qin
Xunzhao Zhou
Junjie Chen
Shang Yi
Qiuli Chen
Limei Huang
Qinle Zhang
Biyan Chen
Jingsi Luo

Publication Date

9-11-2023

Journal

Molecular Genetics & Genomics Medicine

Abstract

BACKGROUND: Homozygous or compound heterozygous ROBO3 gene mutations cause horizontal gaze palsy with progressive scoliosis (HGPPS). This is an autosomal recessive disorder that is characterized by congenital absence or severe restriction of horizontal gaze and progressive scoliosis. To date, almost 100 patients with HGPPS have been reported and 55 ROBO3 mutations have been identified.

METHODS: We described an HGPPS patient and performed whole-exome sequencing (WES) to identify the causative gene.

RESULTS: We identified a missense variant and a splice-site variant in the ROBO3 gene in the proband. Sanger sequencing of cDNA revealed the presence of an aberrant transcript with retention of 700 bp from intron 17, which was caused by a variation in the noncanonical splicing site. We identified five additional ROBO3 variants, which were likely pathogenic, and estimated the overall allele frequency in the southern Chinese population to be 9.44 × 10

CONCLUSION: This study has broadened the mutation spectrum of the ROBO3 gene and has expanded our knowledge of variants in noncanonical splicing sites. The results could help to provide more accurate genetic counseling to affected families and prospective couples. We suggest that the ROBO3 gene should be included in the local screening strategy.

Keywords

Humans, Receptors, Immunologic, Receptors, Cell Surface, Ocular Motility Disorders, Scoliosis, Prospective Studies, Paralysis, allele frequency, HGPPS, noncanonical splicing site, ROBO3, screening strategy

Comments

Supplementary Materials

PMID: 37330975