关键词: EIF 2 S 3基因； MEHMO综合征； 临床表型； 遗传分析

Abstract: Objective To explore the clinical and genetic characteristics of MEHMO syndrome. Methods The clinical data of MEHMO syndrome in 2 children were analyzed retrospectively, and the related literatures were reviewed. Results Both cases were male. Case 1 was admitted at 2 years and 3 months of age. He presented with epileptic seizure, mental retardation, progressive spastic tetraplegia, microcephaly, facial deformity, short stature, and cryptorchidism. Case 2 visited at the age of 3 months and died at the age of 4 months and 15 days. The child presented with recurrent hypoglycemia, microcephaly, small penis, persistent and refractory epilepsy. Both cases had lactic acidosis, and MRI showed thin corpus callosum. There was a missense mutation of c.137 C>T (p.Thr46 Ile) in EIF 2 S 3 gene in case 1 , and a frameshift mutation of c.1391 _c.1394 delCAAT (p.T464 Tfs* 5 ) in EIF 2 S 3 gene in case 2 . These two mutations have not been included in the human genetic variation database (HGMD), and both were classified as pathogenic by American College of Medical Genetics and Genomics (ACMG) classification. Five foreign literatures were retrieved, including 18 patients. There were five EIF 2 S 3 gene mutation sites, one frameshift mutation and four missense mutations, all of which were hemizygous mutations. Patients with frameshift mutation showed all important phenotypes of MEHMO syndrome, such as mental retardation, epilepsy, genital dysplasia, microcephaly, obesity, stunting and hypoglycemia, while patients with missense mutation showed parts of phenotypes and mild symptoms. Conclusion There is a certain genotype-phenotype correlation in MEHMO syndrome. Two cases of MEHMO syndrome in Chinese population were reported for the first time, and two new mutation sites of EIF 2 S 3 gene were found.

Key words: EIF 2 S 3 gene; MEHMO syndrome; clinical phenotype; genetic analysis