Clinical characterization and WAC gene mutation profiling of DeSanto-Shinawi encephalopathy / 中华实用儿科临床杂志

ABSTRACT

Objective:To report the second Chinese DeSanto-Shinawi syndrome (DESSH) case and to summarize the clinical characteristics and WAC gene mutation profiling in all published cases. Methods:A retrospective analysis was performed to evaluate the clinical characteristics and growth and development of a child with DESSH who had been regularly followed up in the Xiangyang No. 1 People′s Hospital, Hubei Medical College and Tianyou Hospital Affiliated to Wuhan University of Science and Technology.The relevant literature was reviewed to assess the relationship between clinical phenotype and spectrum of WAC gene mutation. Results:The female baby with DESSH was regularly evaluated for growth and development till the present age of 1 year and 3 months.She presented with growth and mental retardation, hypotonia, facial dysmophism and microcephaly.Whole-exome sequencing revealed a new de novo pathogenic mutation in the WAC gene (c.1090dupA, p.Arg364Lysfs*14) that has not been reported before.Analysis of 31 reported DESSH cases from 29 families showed that all of them had nonsense mutations or frame-shift mutations in WAC gene, which resulted in the loss of the coiled-coil region of WAC.Twenty-five cases (88.6%) were new mutations of WAC, and 6 cases (19.4%) were chimeric inheritance of gonad.Only 35.5% of them simultaneously lost both the WW domain in truncated WAC protein. Conclusions:DESSH is characterized by facial dysmophism, overall developmental delay and epileptic encephalopathy.This second Chinese DESSH baby was severe with an earlier onset and caused by a new mutation in WAC gene.All DESSH is caused by nonsense mutations or frameshift mutations of WAC gene resulting in the loss of coiled-coil region.There is no significant corresponding phenotype-genotype correlations in those DESSH cases.