IMPE Abstracts

Objective: To analyze the clinical manifestations and genetic characteristics of X-linked intellectual disability (XLID). Methods: The clinical data of a boy with XLID were retrospectively analyzed. The Clinical and gene mutation characteristics of XLID were summarized by a literature review. The whole exome-sequencing test was used to analyze the gene mutation. The pathogenicity of novel mutations was analyzed and the changes of protein function resulted from the candidate mutations were predicted. Results: The boy had global developmental delay, short stature and facial dysmorphism. The whole exome-sequencing test identified a de novo hemizygous variant c.12227C＞G (p.Pro4076Arg) in HUWE1 gene of the patient. This mutation was reported for the first time and is probably pathogenic. Dynamut analysis showed that the mutation reduced the flexibility of the HECT domain. 51 patients with a mutation in HUWE1 gene were mainly characterized by intellectual disability(46/50,92%)， global motor delay(31/37,84%), speech dysfunction(35/42,83%) and short stature(29/37,78%). Among them, there were 25 missense mutations, 2 code shift mutations, 21 patients with 11 mutations located in the HECT domain, were characterized by moderate to severe intellectual disability(21/21,100%) and typical facial dysmorphism consisting of deep set eyes(13/14,93%), blepharophimosis(14/15,93%) and epicanthus(11/13,85%). Conclusion: Patients with HUWE1 mutation located in the HECT domain had a more severe phenotype and recognizable facial features. Patients with clinical manifestations of intellectual disability, short stature and facial dysmorphism should be considered as XLID and a gene test can confirm the diagnosis.