Novel Homozygous FAN1 Mutation in a Familial Case of Karyomegalic Interstitial Nephritis

Abstract

Karyomegalic interstitial nephritis (KIN) is a rare genetic kidney disease associated with a mutation in FAN1 gene and is often underdiagnosed. The histomorphology demonstrates chronic interstitial nephritis with tubular epithelial cells showing bizarre enlarged nuclei. We present a case report of a 47-year-old multiparous South-Indian woman presenting with bilateral pitting pedal oedema and mild hypertension. At the time of presentation, her serum creatinine was 1.52 mg/dL and urine analysis showed mild proteinuria. Kidney biopsy showed features of tubular injury with bizarre enlarged nuclei and focal mild chronic tubulointerstitial nephritis. Immunohistochemistry was negative for cytomegalovirus (CMV) Ag and SV40 Ag. Real-time polymerase chain reaction (PCR) done for CMV and BK virus genomes was negative. Relevant family history was that her older brother was also diagnosed with kidney failure and is on renal replacement therapy. Genetic analysis for FAN1 gene of the proband and her sibling showed two rare mutations of the FAN1 gene in the exon 4, of which, one is non-synonymous mutation and the other is a stop-gain mutation in the proband. This case illustrates a rare presentation of karyomegalic interstitial nephritis in siblings with previous unknown FAN1 gene mutations.

Keywords: FAN1 mutation; interstitial nephritis; karyomegay.

Figure 1

Tubular epithelial cells showing karyomegalic nuclei (H and E 200X)

Figure 2

Electropherogram of the proband and her older brother along with a control, showing FAN1 homozygous mutations in exon 4