Identification of a Frameshift Mutation in SON Gene via Whole Exome Sequencing in a Patient With ZTTK Syndrome

Abstract

Abstract Backgrounds: Since the association between SON gene and Zhu-Tokita-Takenouchi-Kim (ZTTK, OMIM 617140) is formally recognized, the purpose of this study is to detailed report a Chinese girl with clinical features and SON variant. The other aim is to review the previously published papers of ZTTK syndromes to summarize the clinical and genetic characteristics to provide guidance for the ZTTK diagnosis.Case presentations: We report a Chinese girl with typically clinical features of ZTTK syndrome: intellectual disability, developmental delay, cerebral cortex’s aberrations, epilepsy, vision problems, musculoskeletal abnormalities and congenital malformations. Then, the whole exome sequencing (WES) analysis showed that the child had a heterozygous mutation c.5753_5756delTTAG (p. Val1918Glufs*87) in exon 3 of SON gene, which was verified by Sanger sequence, lead to the loss of function of SON protein. Conclusions: We predicted that the heterozygous mutation c.5753_5756delTTAG (p. Val1918Glufs*87) in exon 3 of SON gene caused the ZTTK syndrome, and also was a very hot-spot mutation of SON gene. Further, the summary of all the patients with ZTTK syndromes in clinical, neuroimaging and genetics characteristics could provide guidance for the ZTTK syndrome’s diagnosis.