Identification of a novel variant causing LESKRES in a Chinese family with intellectual disability.

BACKGROUND

Lessel-Kreienkamp syndrome (LESKRES, MIM #619149), an autosomal dominant genetic disorder caused by variants in (MIM*606229), primarily leads to neurodevelopmental symptoms.

OBJECTIVE

This study aims to investigate the genetic etiology of a family with intellectual disability.

METHODS

Whole-exome sequencing (WES) was used to initially identify the pathogenic variants responsible for the intellectual disability in the family, and Sanger sequencing was employed for confirmation. Complete family information was collected, and Sanger sequencing was performed to confirm the co-segregation of the variant with the intellectual disability, thereby determining the pathogenicity of the novel variant. The pathogenicity of the novel variant was evaluated using methods.

RESULTS

All four intellectual disability individuals carried the novel (NM_012154.5): c.2149T>C (p.Cys717Arg) variant, while the other individuals did not. According to ACMG guidelines, this novel variant is classified as likely pathogenic. The novel variant occurs at a conserved position in and is predicted to affect the 3D structure of the protein.

CONCLUSION

This study identifies a novel variant causing LESKRES in the Chinese population for the first time. Our findings expand the variants spectrum of leading to LESKRES and highlight the value of WES in diagnosing genetic causes of intellectual disabilities.