Cyclosporine A Treatment of Proteinuria in a New Case of MAFB-Associated Glomerulopathy without Extrarenal Involvement: A Case Report

Abstract

The <i>MAFB</i> gene encodes an important basic leucine zipper transcription factor that functions in glomerular podocytes, macrophages, and osteoclasts. Recently, <i>MAFB</i> was identified as the gene that was responsible for causing nephropathy with focal segmental glomerulosclerosis (FSGS) with multicentric carpotarsal osteolysis (MCTO) or Duane retraction syndrome (DRS). Here, we describe a patient with nephropathy associated with FSGS who exhibited a novel stop-gain variant in the <i>MAFB</i> gene (NM_005461:c.590C>A (p.Ser197Ter)). The patient’s father exhibited proteinuria with FSGS with possible DRS, whereas the patient exhibited nephropathy with FSGS and nearly normal eye movement and hearing function, as well as intact bone structure in the extremities. Conventional oral steroids or immunosuppressive drugs have not demonstrated effectiveness for patients with nephropathy who exhibit pathogenic variants in <i>MAFB</i>, except for a patient with nephropathy with FSGS and MCTO who experienced attenuated proteinuria within the subnephrotic range in response to cyclosporine A (CyA) treatment for at least 4 years. Thus, we attempted administration of CyA in our patient. Unexpectedly, the patient demonstrated good and rapid responses to CyA, including a partial reduction in proteinuria from approximately 2.0 g/g Cr to proteinuria within the subnephrotic range (0.27 g/g Cr) after 13 months of observation. Our findings suggest that CyA may be a suitable treatment option for patients with nephropathy with FSGS who exhibit pathogenic <i>MAFB</i> variants.

Multicentric Carpotarsal Osteolysis Syndrome Associated Nephropathy: Novel Variants of MAFB Gene and Literature Review

“…So far, one patient with clinical diagnosis of MCTO was reported having partial remission of proteinuria after CyA administration at 1 year of follow-up [ 22 ]. Similar results were reported for the subject with FSGS-DURS3 treated with CyA [ 23 ]. To the best of our knowledge, we report for the first time a case of MCTO with complete remission of proteinuria after administration of CyA.…”

An unusual manifestation in a pediatric patient with MAFB mutation: Sacroiliitis in multicentric carpotarsal osteolysis syndrome

“…Duane retraction syndrome is an eye movement abnormality, resulting in the limitation of the eye to move outward. 13 However, our patient lacks both the presence of an abnormal eye movement disorder in ophthalmological examination and a positive family history. Despite the unresponsiveness to the antirheumatic drugs for joint symptoms F I G U R E 2 Conventional radiography of the patient shows the total loss of carpal bones and erosions of distal ulna and radius (A) and complete loss of tarsal bones (B).…”

“…Patients with MAFB mutations may also represent a distinct feature with autosomal dominant inheritance, Duane retraction syndrome accompanied by focal segmental glomerulosclerosis. Duane retraction syndrome is an eye movement abnormality, resulting in the limitation of the eye to move outward 13 . However, our patient lacks both the presence of an abnormal eye movement disorder in ophthalmological examination and a positive family history.…”

“…of MCTO, it has been recently revealed that renal manifestations in this entity may respond to immunosuppressive medication, cyclosporin A. 13 Although there is no experience in MCTO, a trial of cyclosporin A may be utilized in progressive nephropathy of MCTO.…”

Podocyte-specific Transcription Factors: Could MafB Become a Therapeutic Target for Kidney Disease?

“…Five DRS mutations in MAFB have been reported ( 26 , 27 , 36 ). Four are deletions, and the remaining one is a missense variant in the DNA-binding domain that renders binding to the MARE sequence impossible ( Fig.…”