Abstract:

Objective To investigate the clinical features and gene mutation of patients diagnosed with ZTTK syndrome (Zhu-Tokita-Takenouchi-Kim syndrome). Method The clinical data of three cases of ZTTK syndrome were retrospectively analyzed. Whole exome sequencing was applied to analyze the patients' genetic variants, and Sanger sequencing was used to verify the variant loci. Results In this study, 3 patients, aged from 10 months to 3 years and 8 months, had clinical phenotypes of facial dysmorphism, developmental delay, intellectual disability, microcephaly and abnormal muscle tone, abnormal hand joint or foot valgus, pyelonephritis, cryptorchidism and premature closure of cranial suture. In two cases, sulcus widening and cerebral dysplasia were observed on brain MRI. We found de novo variation in SON gene in all three children, c.3020G>A (p.R1007H), c.1195delG (p.V399fsTer1) and c.5753_5756delTTAG (p.V1918EfsTer87). Conclusion This study reports three cases of ZTTK syndrome due to SON gene abnormalities, which expands the mutation spectrum of SON gene. In this paper, we report three cases of ZTTK syndrome, extending the spectrum of mutations in this gene. The clinical manifestations of ZTTK syndrome are of multisystem involvement; whole exome sequencing may help to make a clear clinical diagnosis.

Key words: ZTTK syndrome, SON gene, whole exome sequencing, gene mutation