Diagnosis of a boy with sporadic Alport syndrome using next generation sequencing and literature review / 中华实用儿科临床杂志

ABSTRACT

Objective To study the feasibility of testing three disease-causing genes for Alport syndrome,COL4A3,COL4A4 and COL4AS,in diagnosing patients with sporadic Alport syndrome by using targeted capture and next generation sequencing.Methods The clinical data of a 9-year-old boy suspected with Alport syndrome were collected.Genomic DNA was extracted using standard procedures from the peripheral blood leukocytes of the patient and his parents,respectively.Targeted capture and next generation sequencing and Sanger sequencing were applied to analyze the mutations in the 3 disease-causing genes.Clinical data of cases reported already with autosomal recessive Alport syndrome caused by the mutations in the COL4A4 gene were summarized.Results The patient was presented with neither family history of hematuria nor chronic renal failure.Haematuria and proteinuria were found at the age of 1 year.The patient presented with episodes of macrohaematuria and gradually developed nephrotic-level proteinuria.At the age of 8 years 7 months,bilateral sensorineural hearing loss was diagnosed.So a probable diagnosis of Alport syndrome was postulated.A compound heterozygous pathogenic mutations of 3578-1G ＞ A and 3967 C ＞ T(Q1323X) were identified in the COL4A4 gene in the patient.The mutation of 3578-1G ＞ A was inherited from his father,and the mutation of Q1323X from his mother.The patient was decisively diagnosed with autosomal recessive Alport syndrome.Conclusions The test of COL4A3,COL4A4 and COL4A5 genes can help diagnose patients with sporadic Alport syndrome by using targeted capture and next generation sequencing.