Epstein Syndrome Presenting as Renal Failure in Young Patients

Yap, Desmond Y H; Tse, Kai Chung; Chan, Tak Mao

doi:10.1080/08860220903033708

Cited by 7 publications

(7 citation statements)

References 14 publications

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“…It has become evident that mutations of the MYH9 gene are responsible for the development of glomerulosclerosis [11][12][13][14] and end-stage renal disease. 15,16 Owing to the fact that Myh9 knockout mice are not viable and heterozygous mice show no phenotype, 18,19 we studied the role of zMyh9 in zebrafish larvae via knockdown by morpholino microinjection.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10] All of them are characterized by macrothrombocytopenia accompanied by sensoneural injury, cataracts, Do ¨hle-like inclusions in neutrophils, and glomerular injury. In addition, clinical studies have reported a causal connection between MYH9 mutations and glomerulosclerosis [11][12][13][14] and end-stage renal disease. [15][16] To date, 39 mutations have been found, several of which are associated with severe glomerular syndromes, such as foot process effacement of podocytes, and focal glomerular basement membrane (GBM) thickening and splitting, resulting in proteinuria and finally end-stage renal disease (reviewed by Kopp et al).…”

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confidence: 99%

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Non-muscle myosin IIA is required for the development of the zebrafish glomerulus

Müller

Rumpel

Hradetzky

et al. 2011

Kidney International

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Mutations in the MYH9 gene, coding for the non-muscle myosin heavy chain IIA (NMHC-IIA), are responsible for syndromes characterized by macrothrombocytopenia associated with deafness, cataracts, and severe glomerular disease. Electron microscopy of renal biopsies from these patients found glomerular abnormalities characterized by alterations in mesangial cells, podocytes, and thickening of the glomerular basement membrane. Knockout of NMHC-IIA in mice is lethal, and therefore little is known about the glomerular-related functions of Myh9. Here, we use zebrafish as a model to study the role and function of zNMHC-IIA in the glomerulus. Knockdown of zNMHC-IIA resulted in malformation of the glomerular capillary tuft characterized by few and dilated capillaries of the pronephros. In zNMHC-IIA morphants, endothelial cells failed to develop fenestrations, mesangial cells were absent or reduced, and the glomerular basement membrane appeared nonuniformly thickened. Knockdown of zNMHC-IIA did not impair the formation of podocyte foot processes or slit diaphragms; however, podocyte processes were less uniform in these morphants compared to controls. In vivo clearance of fluorescent dextran indicated that the glomerular barrier function was not compromised by zNMHC-IIA knockdown; however, glomerular filtration was significantly reduced. Thus, our results demonstrate an important role of zNMHC-IIA for the proper formation and function of the glomerulus in zebrafish.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Non-muscle myosin IIA is required for the development of the zebrafish glomerulus

Müller

Rumpel

Hradetzky

et al. 2011

Kidney International

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“…The reports of renal histology obtained from 14 ADM9 patients have shown a range of findings, summarized in Table 1. 1,10–18 To be sure, this compilation may not include all published cases and has major shortcomings: multiple pathologists reading the biopsies, brief descriptions, and varied terminologies. Nevertheless, there may be important lessons that can be learned.…”

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confidence: 99%

Glomerular pathology in autosomal dominant MYH9 spectrum disorders: what are the clues telling us about disease mechanism?

Kopp

2010

Kidney International

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Genetic variation in MYH9, encoding non-muscle heavy chain IIA, has been recognized for over a decade as the cause of an autosomal dominant syndrome characterized by macrothrombocytopenia, neutrophil inclusions, and glomerular pathology. More recently, genetic variation in the MYH9 region on chromosome 22 has been associated with chronic kidney disease in African-descent individuals. A better understanding of the disease mechanisms responsible for glomerular injury in autosomal dominant MYH9 syndromes will lead to fuller appreciation of the role of this gene in glomerular biology.

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“…The exact renal prognosis is thus largely unknown, and probably highly variable among patients with MYH9 mutations, even though genotype–phenotype correlations have been described [10]. In previous reports as well as in our study, renal outcome was very heterogeneous and unpredictable [4, 5, 12, 13, 15, 19–21, 24, 27, 28, 32–35]. As shown in Table 6 listing available data on renal outcome from reported cases of MYH9 nephropathy, we cannot assert that usual prognostic factors of renal outcome (such as baseline eGFR, the degree of proteinuria and hypertension) are applicable in MYH9-RD.…”

Section: Discussionmentioning

confidence: 63%

“…Data reported, when available, from all the reported cases of MYH9 nephropathy in our knowledge and our case series [4, 5, 12, 13, 15, 20–22, 24, 27, 32–35]. Age, CKD stages, follow-up duration, eGFR slope are expressed in median (range) values.…”

Section: Discussionmentioning

confidence: 99%

MYH9-related disorders display heterogeneous kidney involvement and outcome

Tabibzadeh

Fleury

Labatut

et al. 2018

Clinical Kidney Journal

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BackgroundMYH9-related diseases (MYH9-RD) are autosomal dominant disorders caused by mutations of the MYH9 gene encoding the non-muscle myosin heavy chain IIA. They are characterized by congenital thrombocytopenia, giant platelets and leucocyte inclusions. Hearing impairment, pre-senile cataract and nephropathy can also occur. We aimed to evaluate renal involvement and outcome in MYH9-RD patients followed-up by nephrologists.MethodsWe conducted a retrospective multicentre observational study of 13 patients among 9 families with MYH9 mutation diagnosed by genetic testing and immunofluorescence assay referred to nephrologists.ResultsAt initial referral, median age was 30 (range 14–76) years. Median estimated glomerular filtration rate was 66 mL/min/1.73 m2 (0–141) and two patients had already end-stage renal disease (ESRD). Renal presentation associated proteinuria (n = 12), haematuria (n = 6) and hypertension (n = 6). Three patients developed a rapid onset ESRD whereas five others had a relatively stable kidney function over a 3-year median follow-up (1–34). Extra-renal features varied widely, with hearing impairment in six patients, cataract in two and mild liver dysfunction in seven. Thrombocytopenia existed at referral in 11 patients. Time to diagnosis varied from 0 to 29 years (median 3 years). Initial diagnoses such as idiopathic thrombocytopenic purpura (n = 4) and focal segmental glomerulosclerosis (n = 1) led to corticosteroid administration (n = 4), intravenous immunoglobulins (n = 3), cyclophosphamide (n = 1) and splenectomy (n = 1).ConclusionsRenal involvement and outcome in MYH9-RD are heterogeneous. The diagnosis is often delayed and misdiagnoses can lead to unnecessary treatments. MYH9-RD should be considered in any patient with glomerular involvement associated with a low or slightly decreased platelet count and/or hearing loss and liver dysfunction.

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Epstein Syndrome Presenting as Renal Failure in Young Patients

Cited by 7 publications

References 14 publications

Non-muscle myosin IIA is required for the development of the zebrafish glomerulus

Non-muscle myosin IIA is required for the development of the zebrafish glomerulus

Glomerular pathology in autosomal dominant MYH9 spectrum disorders: what are the clues telling us about disease mechanism?

MYH9-related disorders display heterogeneous kidney involvement and outcome

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