Letter to the Editor: “Two Cases with Horseshoe Kidney in Association with Nephrotic Syndrome: Is There a Causal Relationship between Two Conditions?”

Kayataş, Mansur; Ürün, Yüksel

doi:10.1080/08860220701278133

Cited by 8 publications

(8 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Horseshoe kidneys can lead to vesicoureteral reflux, a known association with FSGS, but reflux was not observed in this patient[12, 13]. An independent association between horseshoe kidneys and FSGS has not yet been found, as there have only been a few case reports presenting these two conditions together[14, 15]. …”

Section: Discussionmentioning

confidence: 83%

Functional Validation of an Alpha-Actinin-4 Mutation as a Potential Cause of an Aggressive Presentation of Adolescent Focal Segmental Glomerulosclerosis: Implications for Genetic Testing

et al. 2016

View full text Add to dashboard Cite

Genetic testing in the clinic and research lab is becoming more routinely used to identify rare genetic variants. However, attributing these rare variants as the cause of disease in an individual patient remains challenging. Here, we report a patient who presented with nephrotic syndrome and focal segmental glomerulosclerosis (FSGS) with collapsing features at age 14. Despite treatment, her kidney disease progressed to end-stage within a year of diagnosis. Through genetic testing, an Y265H variant with unknown clinical significance in alpha-actinin-4 gene (ACTN4) was identified. This variant has not been seen previously in FSGS patients nor is it present in genetic databases. Her clinical presentation is different from previous descriptions of ACTN4 mediated FSGS, which is characterized by sub-nephrotic proteinuria and slow progression to end stage kidney disease. We performed in vitro and cellular assays to characterize this novel ACTN4 variant before attributing causation. We found that ACTN4 with either Y265H or K255E (a known disease-causing mutation) increased the actin bundling activity of ACTN4 in vitro, was associated with the formation of intracellular aggregates, and increased podocyte contractile force. Despite the absence of a familial pattern of inheritance, these similar biological changes caused by the Y265H and K255E amino acid substitutions suggest that this new variant is potentially the cause of FSGS in this patient. Our studies highlight that functional validation in complement with genetic testing may be required to confirm the etiology of rare disease, especially in the setting of unusual clinical presentations.

show abstract

Section: Discussionmentioning

confidence: 83%

Functional Validation of an Alpha-Actinin-4 Mutation as a Potential Cause of an Aggressive Presentation of Adolescent Focal Segmental Glomerulosclerosis: Implications for Genetic Testing

et al. 2016

View full text Add to dashboard Cite

show abstract

“…It is frequently associated with anomalies of other systems in which genetic factors may play a common etiological role, including musculoskeletal, cardiovascular, and gastrointestinal systems, as well as in certain neurological conditions (23). The occurrence of glomerulonephritis in horseshoe kidney has already been reported (24)(25)(26)(27), with focal and segmental glomerulosclerosis described in two cases (25,27).…”

Section: Discussionmentioning

confidence: 99%

Frasier syndrome: four new cases with unusual presentations

Guaragna

Lutaif

Bittencourt

et al. 2012

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

SUMMARYFrasier syndrome (FS) is characterized by gonadal dysgenesis and nephropathy. It is caused by specific mutations in the Wilms' tumor suppressor gene (WT1) located in 11p23. Patients with the 46,XY karyotype present normal female genitalia with streak gonads, and have higher risk of gonadal tumor, mainly, gonadoblastoma. Therefore, elective bilateral gonadectomy is indicated. Nephropathy in FS consists in nephrotic syndrome (NS) with proteinuria that begins early in childhood and progressively increases with age, mainly due to nonspecific focal and segmental glomerular sclerosis (FSGS). Patients are generally unresponsive to steroid and immunosuppressive therapies, and will develop end-stage renal failure (ESRF) during the second or third decade of life. We report here four cases of FS diagnosis after identification of WT1 mutations. Case 1 was part of a large cohort of patients diagnosed with steroid-resistant nephrotic syndrome, in whom the screening for mutations within WT1 8-9 hotspot fragment identified the IVS9+5G>A mutation. Beside FS, this patient showed unusual characteristics, such as urinary malformation (horseshoe kidney), and bilateral dysgerminoma. Cases 2 and 3, also bearing the IVS9+5G>A mutation, and case 4, with IVS9+1G>A mutation, were studied due to FSGS and/or delayed puberty; additionally, patients 2 and 4 developed bilateral gonadal tumors. Since the great majority of FS patients have normal female external genitalia, sex reversal is not suspected before they present delayed puberty and/or primary amenorrhea. Therefore, molecular screening of WT1 gene is very important to confirm the FS diagnosis. Arq Bras Endocrinol Metab. 2012;56(8):525-32 SUMÁRIO A síndrome de Frasier (SF), caracterizada por disgenesia gonadal e nefropatia, é causada por mutações específicas no gene supressor do tumor de Wilms (WT1) localizado em 11p23. Pacientes com cariótipo 46,XY apresentam genitália feminina normal com gônadas disgenéticas e alto risco de tumor gonadal, principalmente o gonadoblastoma. Por isso, a gonadectomia bilateral eletiva está indicada. A nefropatia na SF consiste de síndrome nefrótica com proteinúria que se inicia na infância e aumenta progressivamente com a idade, principalmente devido à glomeruloesclerose focal e segmentar (GESF). Esses pacientes não respondem ao tratamento com esteroides e imunossupressores e desenvolverão insuficiência renal crônica durante a segunda ou terceira década de vida. Neste trabalho, são relatados quatro casos de SF cujo diagnóstico foi definido após o rastreamento molecular do gene WT1. O caso 1 faz parte de um grande grupo de pacientes que tiveram diagnóstico de síndrome nefrótica corticorresistente e no qual o rastreamento de mutações no fragmento 8-9 do gene WT1 identificou a mutação IVS9+5G>A. Além da SF, essa paciente apresentou características incomuns, tais como malformação urinária (rins em ferradura) e disgerminoma bilateral. Os casos 2 e 3 também apresentaram a mutação IVS9+5G>A, e, no caso 4, foi identificada a mutação IVS9+1G>A, sendo que esse...

show abstract

“…In the literature, glomerular diseases in HSK (Table ) reported are, respectively, membranous nephropathy, focal and segmental glomerulosclerosis, membranoproliferative glomerulonephritis, mesangioproliferative glomerulonephritis, and renal amyloidosis . To the best of our knowledge, we are the first to describe the cases of IgA nephropathy or Henoch‐Schonlein purpura nephritis (secondary IgA nephropathy) occuring in a HSK.…”

Section: Discussion and Literature Reviewmentioning

confidence: 92%

Immunoglobulin A nephropathy in horseshoe kidney: Case reports and literature review

Jin

Chen

et al. 2014

Nephrology

View full text Add to dashboard Cite

This is a valuable report describing two cases with IgA nephropathy on horseshoe kidneys. The authors discuss past reports and emphasize the importance of renal biopsy for horseshoe kidney patients with heavy proteinuria. ABSTRACT:Horseshoe kidney is the most common congenital renal fusion anomaly. Immunoglobulin A nephropathy is a common glomerulonephritis worldwide. However, the co-occurrence of these diseases had not been reported in the literature. We report the first two cases with the occurrence of immunoglobulin A nephropathy in horseshoe kidney. The first case was a 26-yearold male with hypertension and proteinuria (1.4 g/24 h), his pathological finding was primary immunoglobulin A nephropathy. The second case was a 15-year-old female who presented with recurrent peliosis on bilateral lower extremities, haematuria and proteinuria (1.7 g/24 h). Her renal biopsy finding was Henoch-Schonlein purpura nephritis (secondary immunoglobulin A nephropathy). In both cases, renal biopsy was performed by experienced doctors under ultrasonic guidance at the renal upper pole and no postoperative complications were observed. After they were treated based on the renal pathological findings for 6 months, urine protein excretion decreased significantly and blood pressure and serum creatinine stabilized. It is possible that immunoglobulin A nephropathy occurs in a horseshoe kidney patient. Renal biopsy may be valuable and viable for horseshoe kidney patients with heavy proteinuria to identify pathologic type of glomerulopathy and to guide treatment, if renal biopsy is performed by experienced doctors at the renal upper pole under renal ultrasonic guidance.

show abstract

Letter to the Editor: “Two Cases with Horseshoe Kidney in Association with Nephrotic Syndrome: Is There a Causal Relationship between Two Conditions?”

Cited by 8 publications

References 7 publications

Functional Validation of an Alpha-Actinin-4 Mutation as a Potential Cause of an Aggressive Presentation of Adolescent Focal Segmental Glomerulosclerosis: Implications for Genetic Testing

Functional Validation of an Alpha-Actinin-4 Mutation as a Potential Cause of an Aggressive Presentation of Adolescent Focal Segmental Glomerulosclerosis: Implications for Genetic Testing

Frasier syndrome: four new cases with unusual presentations

Immunoglobulin A nephropathy in horseshoe kidney: Case reports and literature review

Contact Info

Product

Resources

About