RESUMEN
OBJECTIVE@#To analyze the clinical characteristics and genetic basis of two children patients with CHARGE syndrome.@*METHODS@#The clinical features of the two patients were analyzed, and potential variants were detected by Trio whole exome sequencing (trio-WES) of the probands and their parents.@*RESULTS@#Child 1 has manifested cerebellar vermis dysplasia, enlargement of cerebral ventricles, whereas child 2 manifested with infantile spasm and congenital hip dysplasia. Both children were found to harbor de novo heterozygous variants of the CHD7 gene, namely c.4015C>T (exon 17) and c.5050G>A (exon 22). Based on the guidelines of the American College of Medical Genetics and Genomics, the two variants were rated as pathogenic variants, and the related disease was CHARGE syndrome. Furthermore, child 2 was also found to harbor a novel heterozygous c.6161A>C (p.Gln2054Pro) missense variant of COL12A1 gene, which was rated as possibly pathogenic, and the associated disease was Bethlem myopathy type 2, which is partially matched with the patient' s clinical phenotype.@*CONCLUSION@#The special clinical phenotypes shown by the two children harboring novel CHD7 variants have further expanded the phenotypic spectrum of CHARGE syndrome.
Asunto(s)
Humanos , Síndrome CHARGE/genética , ADN Helicasas/genética , Proteínas de Unión al ADN/genética , Pruebas Genéticas , Heterocigoto , Mutación , Fenotipo , Secuenciación del ExomaRESUMEN
Congenital disorder of glycosylation (CDG) is a group of genetic metabolic diseases involving multiple organs. A case of CDG caused by SLC35A2 gene mutation was diagnosed. The clinical characteristics included spasms, developmental retardation and multiple malformations. Video-electroencephalogram showed dysrhythmia. A de novo heterozygous missense mutation of SLC35A2 gene was detected by whole exome sequencing: c.844G>A (p.Gly282Arg). It was predicted to be likely pathogenic according to American College of Medical Genetics and Genomics guidelines which had not been reported in China.