Abstract:

Objective To investigate the clinical phenotypes and genetic characteristics of Witteveen-Kolk syndrome caused by switch-insensitive 3 transcription regulator family member A(Sin3A) variation. Methods The clinical data of a child with developmental delay were collected，and whole-exome sequencing was used to determine the child and his parents. The suspected variations were verified by Sanger sequencing. The clinical characteristics and variation characteristics of Witteveen-Kolk syndrome were analyzed based on literature. Results The main clinical manifestations of Witteveen-Kolk syndrome were mild to moderate mental retardation or developmental delay，special facial features(long face，prominent forehead，sunken nose bridge，long philtrum) and short stature. Brain magnetic resonance imaging (MRI) showed different degrees of brain malformations. Sin3A c.803dupC(p.Leu269Thrfs*37)(heterozygous) frameshift variation was found by whole-exome sequencing. Sanger sequencing showed that the parents of the child had normal genotypes at this locus. The variation was not included in gnomAD and other control population databases，which was classified as "pathogenic" variation according to American College of Medical Genetics and Genomics(ACMG)/the Association for Molecular Pathology(AMP)variation classification criteria. Conclusions Sin3A variation can lead to Witteveen-Kolk syndrome. Genetic testing can confirm the etiology diagnosis of children with developmental delay and special facial features.

Key words: Switch-insensitive 3 transcription regulator family member A gene, Whole-exome sequencing, Witteveen-Kolk syndrome, Mental retardation, Developmental delay