关键词: 高通量测序, 基因突变, 遗传性综合征

Abstract: Objective: To identify the type and pattern of gene mutation of a developmental delayed child and her family members via gene mutation analysis for the accurate diagnosis of disease in this patient. Methods: Peripheral blood DNA was extracted from the proband as well as her family members - father and mother, and gene mutation screening was performed by high throughput sequencing. The pathogenic candidate genes were identified according to the clinical phenotype data combined with the results of gene mutation screening. Sanger sequencing technology was used to validate the pathogenic mutation sites of proband and her family pedigree. Results: Heterozygous missense variants in MECP2 gene and PTPN11 gene were identified in proband by high throughput sequencing, which were c.398G> A, p.Arg133His and c.188A> G, p.Tyr63Cys, respectively. Sanger sequencing revealed that the MECP2 gene mutation leading to Rett syndrome in proband was inherited from her mother and the PTPN11 gene mutation leading to Noonan syndrome was from her father. The two missense variations detected were pathogenic variants in concordance with the clinical phenotype of the proband, her mother and father, respectively. Conclusions: In this study, two pathogenetic variants are identified in the developmental delayed child by high-throughput sequencing, leading to the occurrence of two different hereditary syndrome in the same patient. It is suggested that two or more phenotypes of disease may be present in the same patient, and attention should be paid to this posibility.

Key words: High throughput sequencing, Gene mutation, Hereditary syndrome