Circulating tumor cells (CTC) and circulating tumor DNA(ctDNA)are cancer cells that detach from their primary site to circularity system or other body fluids,which hold the promise of monitoring of tumor evolution and therapeutic efficacy and improving prognosis for patients.With the rapid development of detection technologies of CTCs and ctDNA,the sensitivity and specificity of current assays had significant improved.CTCs can be detected by use of cytometry,immunofluorescence analysis and genedetection and the detection methods of ctDNA mainly based on PCR and the next generation sequencing.As the developing of various methods and platforms were developed for detecting the circulating tumor cells and circulating tumor DNA,it is necessary to use the detection technology flexibly according to the research purpose and provide more assistance for the diagnosis and treatment of tumor.

Objective: Alport syndrome was an inherited kidney disease caused by the mutation of COL4A3, COL4A4, or COL4A5. Whole-exome sequencing was used to detect the mutations on these genes for the molecular diagnosis of Alport syndrome. Methods: A 6-year-old girl found accidentally with microscopic hematuria at the age of 4. The clinical data and blood sample of the family including proband, parents, brothers, and sisters were collected. Whole exome sequencing was conducted using their genomic DNAs. Results: A novel heterozygous frameshift mutation c.1826delC (p.Pro609Glnfs*44) was found in the exon 25 of the COL4A4 (NM_000092) in the proband, the father, and the sister, showing an autosomal dominant inheritance pattern of Alport syndrome. This mutation of COL4A4 was confirmed by mutation analysis, and the mutation of c.1826delC was verified by Sanger sequencing. No mutations on COL4A3 and COL4A5 were detected in this family. And the mother and brother are normal wide-type. Conclusions This novel mutation is a valuable addition to the current genetic profile of Alport syndrome, and provide us a better understanding of the disease. Whole-exome sequencing is a power tool to identify the novel mutations of inherited disease and contribute to the molecular diagnosis of disease.