Searching for Significance in Oceania: A Voyage of Recurrent FSGS in a Patient from the Marshall Islands with Variants of Uncertain Significance
- Diversity and Equity: Other Research
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diversity and Equity in Kidney Health
- 900 Diversity and Equity in Kidney Health
- Mignano, Salvatore E., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Lau, Rhiana L.A., Kapiolani Medical Center for Women and Children, Honolulu, Hawaii, United States
- Izutsu, Christie H., Queen's Medical Center, Honolulu, Hawaii, United States
- Kim, Lisa, Queen's Medical Center, Honolulu, Hawaii, United States
The success of next generation exome sequence analysis has dependency on clinical and pathologic phenotypic correlation. There is a gap in knowledge of genetic variants in glomerulopathy unique to those referred to the Pacific Basin's single adult organ transplantation program. The effects of the U.S. Nuclear Weapons Testing Program (USNWTP) in the Bikini Atoll between 1946-1958 with aggregate detonation of "7,200 Hiroshima atomic bombs" are unknown for the relocated inhabitants. We present a case of recurrent FSGS with unusual mesangial IgM predominant deposits and associated variants of uncertain significance.
The patient is a 21 year old female from the Marshall Islands with history of deceased donor renal transplant 3 years prior who presents with increased proteinuria. Renal biopsy showed no evidence of rejection but segmental sclerosis with IgM positivity in a membranoproliferative pattern along with diffuse mesangial C4d positivity with electron dense deposits (Figure 1). Review of history showed she was diagnosed with FSGS on biopsy in the Philippines at age 16 then relocated to Honolulu, Hawaii where she was evaluated by pediatric nephrology. Results from KidneySeqtmv3.0 (Figure 2) revealed heterozygous variants of uncertain significance. Two were in XPO5 (exportin-5), variants of which have been associated with autosomal recessive FSGS, one in NPHS2 (podocin), and a variant in CUBN, a receptor on intestinal mucosa with high affinity binding to APOA1/HDL and intrinsic factor-vitamin B12.
We demonstrate the possibility of a recurrent glomerulopathy due to circulating factor rather than donor related disease. VUS analysis must be made alongside biopsy phenotype correlation for greatest benefit. Patients most in need of equity in health and technology must also be included in gene variant databases.
From left to right, light microscopy, IgM, C4d, electron microscopy