Expanding the mutational spectrum of ZTTK syndrome: A de novo variant with global developmental delay and malnutrition in a Chinese patient.

Background: Zhu-Tokita-Takenouchi-Kim (ZTTK, OMIM 617140) syndrome is a severe multisystem developmental disorder characterized by intellectual disability, developmental delay, cortical malformations, epilepsy, visual problems, musculoskeletal abnormalities, and congenital malformations. ZTTK syndrome is caused by a heterozygous pathogenic variant of the SON gene (NM_138927) at chromosome 21q22.1. The purpose of this study was to investigate the pathogenesis of a 6-month-old Chinese child who exhibited global developmental delay, muscle weakness, malnutrition, weight loss, and strabismus, brain abnormality, immunological system abnormalities.

Methods: The little girl was tested for medical exome sequencing (MES) and mtDNA sequencing in trio. And, the mutation was validated by Sanger sequencing.

Results: A novel de novo frameshift variant, c.1845_1870del26 (p.G616Sfs*61), in the SON gene was found in the proband.

Conclusion: We described a 6-month-old Chinese child with global developmental delay caused by pathogenic de novo mutation c.1845_1870del26 (p.G616Sfs*61) in the SON. Apart from a founder mutation, we reviewed the phenotypic abnormalities and genotypes in 79 individuals. The data showed that global developmental delay is accompanied by other system disorders. Our findings expanded the mutational spectrum of ZTTK syndrome and provide genetic counseling of baby with global developmental delay.