Detection and analysis of gene mutation in a case of child’s renal coloboma syndrome

Abstract

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 α1 microglobulin index increased. Conclusion The heterozygous mutation c.70dupG (p.V26Gfs*28) in PAX2 is the genetic pathogenic cause for the patient with RCS. Key words: Coloboma; Renal insufficiency; PAX2 gene; Frameshift mutation