A Case of Renal Coloboma Syndrome Caused by Spontaneous Mutation of PAX2 / 罕见病研究

This article reports a case of a child with full-length (paired box family, PAX) PAX2 mutation leading to renal coloboma syndrome. The patient is an 11-year-old boy presented with persistent foamy urine and unexplained renal failure. The boy has suffered from vision decline ever since infancy. Genetic testing confirms the mutation of the PAX2 splice site (c.862-1G > A). Sanger sequencing shows no mutation at this site in his parents and demonstrates a spontaneous mutation. His clinical manifestations also confirms diagnosis of renal coloboma syndrome. The PAX2 mutation was responsible for the boy's progression to end-stage renal disease and extrarenal manifestations.

Papillorenal syndrome and the PAX2 gene / 国际儿科学杂志

Papillorenal syndrome,also known as renal coloboma syndrome,is an autosomal donunant inherited condition typically featured by congenital aplasia of kidneys and eyes,most of which occur in childhood.Studies have revealed that a mutation in PAX2 gene is the critical etiology of Papillorenal Syndrome.The PAX2 gene is located at chromosome 10q23-24,encoding PAX2 protein isoform c,which belongs to the transcription factors family paired box family that regulate downstream gene expression and play an important role in development of organs such as the kidney and the eye.Mutations in PAX2 result in structural and functional abnormality of PAX2 protein isoform c,which leads to the dysplasia of the related organs.More than 80 mutations in the PAX2 gene have been currently reported,causing various clinical phenotypes.The mutational analysis of the PAX2 gene would be of help to direct the diagnosis,monitoring and treatment of papillorenal syndrome.This review summarizes the research progress of papillorenal syndrome and mutations in the PAX2 gene.

Detection and analysis of gene mutation in a case of child's renal coloboma syndrome / 中华眼底病杂志

Objective To analyze and identify the pathogenic mutation that caused a case of child's renal coloboma syndrome (RCS).Methods A child with congenital cataract in the right eye and optic disc defect in the left eye and his parents with normal phenotype were included in the study.The blood of the child and his parents were captured to extract DNA and make molecular test.The possible variants were screened through NGS sequencing using the ophthalmology gene panel on illumina NextSeq 500 platform,and proved the selected PAX2 mutation by Sanger sequencing.Pathogenicity report was retrieved through PubMed and related database.Pathogenicity analysis of the candidate mutated site has careful consideration of the patient's clinical presentations and sequencing result base on Standards and Guidelines for the Interpretation of Sequence Variants revised by ACMG.According to the results of gene diagnosis,the child was executed related clinical examinations on kidney.Results The sequence result showed that a heterozygous mutation in PAX2,c.70dupG (p.V26Gfs*28),which lead to truncated protein product that terminated after 28 amino acids of the mutated site.Both of his normal parents were not carriers of the heterozygous mutation.Sanger sequencing results of the child and his parents were consistent with the NGS sequencing.The autosomal dominant disease phenotype was inferred to be caused by the heterozygous mutation of c.70dupG (p.V26Gfs*28) of PAX2 gene.Renal color Doppler ultrasound results showed the child with small renal cysts on the left and mildly separated collecting system.Renal function tests showed the child with αl microglobulin index increased.Conclusion The heterozygous mutation c.70dupG (p.V26Gfs*28) in PAX2 is the genetic pathogenic cause for the patient with RCS.