Identification of a novel SALL4 variant associated with unilateral renal agenesis and right renal pelvis duplication by prenatal exome sequencing: a case report

TL;DR

A new mutation in the SALL4 gene is linked to kidney abnormalities in a fetus, offering insights for genetic counseling.

Contribution

A novel de novo frameshift mutation in SALL4 is associated with unilateral renal agenesis and renal pelvis duplication.

Findings

A de novo heterozygous mutation c.486_487del in SALL4 was identified in the fetus.

The mutation is predicted to be pathogenic by bioinformatics tools SIFT, PolyPhen-2, and Mutation Taster.

A maternally inherited deletion in the 2q13 region was also detected in the fetus.

Abstract

Congenital renal anomalies are one of the leading causes of perinatal and neonatal mortality in children. Here, we present a case of a 17-week-6-day pregnant patient, in whom prenatal ultrasound confirmed the fetal right duplex kidney and left renal agenesis, leading to termination of pregnancy at the patient's request. Whole-exome sequencing were conducted on the fetus and its parents to identify the cause of the fetal ultrasound abnormalities, followed by validation with Sanger sequencing and CMA/SNP-Array. Bioinformatics analysis assessed the pathogenicity of the mutation site using SIFT, PolyPhen-2, and Mutation Taster. A de novo heterozygous mutation c.486_487del(p.P163Hfs*17) was identified in exon 2 of the SALL4 gene, with neither parent carrying the mutation. The bioinformatics analysis results all support that the mutation is pathogenic. This frameshift mutation results in a complete alteration of the base sequence from the mutation site, leading to an abnormal amino acid translation and subsequent manifestation of the disease phenotype. Additionally, a maternally inherited 698.8 Kb deletion in the 2q13 region (seq[GRCh37] 2q13(110697011_111395836)x1) was detected in the fetus. Our study identified a novel de novo frameshift mutation in exon 2 of the SALL4 gene. This mutation is associated with unilateral renal agenesis and duplication of renal pelvis, providing valuable insights for genetic counseling and prenatal diagnosis of SALL4-related disorders.

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