Abstract:

This study aimed to detect the pathogenic gene variation sites in a rare disease family with neurodevelopmental disorder accompanied by spastic bilateral paralysis and visual deficiency and conduct genetic analysis. The proband presented at Qinzhou Maternal and Child Health Hospital due to severe intellectual disability, language disorder, spastic diplegia, strabismus and special facial features. Clinical data of the proband and family members were collected. The proband’s mother had the same phenotype as the proband and was 23 weeks pregnant, while other family members had no abnormal phenotypes. Peripheral blood samples of family members and amniotic fluid from the proband’s mother were collected, and whole-exome sequencing technology was applied for gene detection. The gene detection results of the proband and his mother indicated a heterozygous mutation c.1759C>T (p.R587*) in exon 11 of the CTNNB1 gene. The proband inherited this variation from his mother with intellectual disability. This variation replaced the cytosine (C) at nucleotide 1759 of the CTNNB1 gene with thymine (T), resulting in the 587th amino acid being changed to a stop codon. Analysis by the SWISS-MODEL software suggested that the mutation site led to a change in the protein structure, resulting in a truncated protein. According to the Standards and Guidelines for the Interpretation of Sequence Variants of the American College of Medical Genetics and Genomics, c.1759C>T (p.R587*) was rated as a pathogenic variation (PVS1+PS2+PM2-Supporting). The mutation was not detected in the proband’s maternal grandparents and father. The amniotic fluid test showed that the fetus did not carry this mutation, and no abnormalities have been found since birth. The heterozygous variation of the CTNNB1 gene in the proband and his mother is considered to be the pathogenic cause of neurodevelopmental disorder accompanied by spastic bilateral paralysis and visual deficiency. Gene detection technology can assist clinicians in disease diagnosis.

Key words: Intellectual disability, Vision disorders, Cerebral palsy, Case reports, CTNNB1 gene