Unilateral polycystic kidney with <i>PKHD1</i> gene mutation

Jeong Hyeon Park; Hyewon Woo; Bum Sang Cho; Hye-Young Kim

doi:10.23876/j.krcp.24.157

A 19-year-old female visited the outpatient clinic to follow up on kidney imaging. She had been diagnosed with incidental left hydronephrosis which was found at fetal ultrasonography and followed yearly until 6 years old, and she had no medical problems including urinary tract infections. There was no family history of kidney disease including cystic disease and her parents’ kidney sonographic findings were normal. Her physical examination findings, blood and urine tests were all normal.

The sonographic finding when she was 2 years old showed only a 0.6 cm-sized simple cyst in the right kidney and severe hydronephrosis of the left kidney, however, dynamic abdominal and pelvic computed tomography (CT) performed at 19-year-old showed innumerable cysts of the right kidney, and residual mild dilatation of left renal pelvocalyx which was thought the sequelae of previous severe hydronephrosis.

CT showed that the left kidney morphology was normal except for the previously diagnosed mild calyceal dilatation, but a polycystic change was found throughout the total right kidney (Fig. 1). A next-generation sequencing (NGS) for polycystic kidney disease confirmed a heterozygous mutation of c.7769T>G, p.(Met2590Arg) in the PKHD1 gene which was a variant of unknown clinical significance (VUS). PKD1, PKD2, and other PCKD-related gene tests were negative (Table 1).

Mutations in PKHD1 are an important cause of autosomal recessive polycystic kidney disease (ARPKD), but the clinical manifestations are diverse. This case has a heterozygote mutation in PKHD1, but as it is a VUS state, there is no clinical problem and it is expected that there will be no genetic abnormality. It is not sure that the left hydronephrosis found in this case can be assumed as occurring due to the influence of this mutation. However, mutations in PKHD1 were also identified in studies analyzing families of ARPKD patients, and it can be explained that previously reported cases of asymptomatic unilateral polycystic kidney disease in adults are also might be partially associated with PKHD1 [1,2]. However, it is still difficult to explain why polycystic nephropathy occurs in only one kidney, and it is believed that the mechanism can be revealed through additional clinical and genetic experiences.

In this case, the PKHD1 gene mutation was confirmed through NGS analysis in an incidentally found unilateral polycystic kidney. Although the unilateral polycystic kidney is not clinically significant, it is necessary to confirm that it is one of the various heterozygotes of the PKHD1 gene.

This report was approved by the Institutional Review Board of Chungbuk National University Hospital (No. 2023-10-014).

Notes

Conflicts of interest

All authors have no conflicts of interest to declare.

Data sharing statement

The data presented in this study are available from the corresponding author upon reasonable request.

Authors’ contributions

Conceptualization, Investigation: JHP, HYK

Data curation: All authors

Formal analysis: JHP

Methodology: HW, BSC

Supervision: HW, HYK

Writing–original draft: JHP, HW

Writing–review & editing: All authors

All authors read and approved the final manuscript.

Figure 1.

Abdominopelvic computed tomography image.

It showed that the left kidney morphology was normal except for the previously diagnosed mild calyceal dilatation, but a polycystic change was found throughout the total right kidney.

Table 1.

Result of next-generation sequencing polycystic kidney disease panel^a and variant interpretation

Gene	Zygosity	Variant	Classification	CADD (hg38 v1.7)	Phenotype	Phenotype MIM No.	Inheritance
PKHD1	Heterozygous	c.7769T>G, p.(Met2590Arg)	VUS	0.912	Polycystic kidney disease 4, with or without hepatic disease	263200	AR
PKD1	Not detected				Polycystic kidney disease 1	173900	AD
PKD2	Not detected				Polycystic kidney disease 2	613095	AD
GANAB	Not detected				Polycystic kidney disease 3	600666	AD
DZIP1L	Not detected				Polycystic kidney disease 5	617610	AR
DNAJB11	Not detected				Polycystic kidney disease 6 with or without polycystic liver disease	618061	AD
HNF1B	Not detected				Renal cysts and diabetes syndrome	137920	AD
ALG8	Not detected				Polycystic liver disease 3 with or without kidney cysts	617874	AD
LRP5	Not detected				Polycystic liver disease 4 with or without kidney cysts	617875	AD

AD, autosomal dominant; AR, autosomal recessive; CADD, combined annotation dependent deletion; MIM, Mendelian inheritance in man; VUS, variant of uncertain significance.

^aGene list included in NGS panel is ANKS6, CEP164, CEP83, COL4A1, DNAJB11, DZIP1L, GANAB, HNF1B, INVS, MAPKBP1, NPHP1, NPHP3, NPHP4, PKD1, PKD2, PKHD1, TMEM67, TSC1, TSC2, TTC21B, UMOD, VHL, WDR19, ALG8, ALG9, CEP290, COL4A4, ETFA, FLCN, LRP5, NOTCH2, PAX2, PMM2, and SEC61A1.

References

1. Gunay-Aygun M, Turkbey BI, Bryant J, et al. Hepatorenal findings in obligate heterozygotes for autosomal recessive polycystic kidney disease. Mol Genet Metab 2011;104:677–681.

2. Cho JM, Park HC, Lee JW, et al. Baseline characteristics of the Korean genetic cohort of inherited cystic kidney disease. Kidney Res Clin Pract 2023;42:617–627.

Unilateral polycystic kidney with PKHD1 gene mutation

Notes

Figure 1.

Abdominopelvic computed tomography image.

Table 1.

References