The New Compound Heterozygous Mutation of NUP Nephropathy: Report of Two Cases and Literature Review

2021 ◽  
Author(s):  
Yuxin Pei ◽  
Liping Rong ◽  
Mengjie Jiang ◽  
Zhilang Lin ◽  
Cheng Cheng ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Literature Review ◽  
End Stage Renal Disease ◽  
Compound Heterozygous ◽  
Founder Mutations ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Renal Manifestation ◽  
Stage Renal Disease ◽  
End Stage

Abstract Backgrounds: NUP nephropathy is identified as a rare monogenic cause of steroid-resistant nephrotic syndrome recently. To explore the relationship between NUP mutation and renal disorders, we provide two cases and a literature review of the genotypical and phenotypical features in patients with NUP nephropathy.Results: We reported two patients with newly diagnosed NUP nephropathy who carried a compound heterozygous mutations in NUP107 and NUP93 gene respectively. Both patients were diagnosed steroid-resistant nephrotic syndrome and progressed to end-stage renal disease in childhood. While the mutation c.1537+1G>A in NUP93 gene was previously described, the mutations c.460A>G and c.1085C>T in NUP107 gene and c.1472A>T in NUP93 gene were novel. We also summarized the phenotypic and genetic spectrum of NUP nephropathy in eighty-six reported patients who carried 50 different mutations in 6 NUP genes (NUP107, NUP93, NUP205, NUP85, NUP133, NUP160). The majority of them were Asians (66/86, 76.7%). The mutation c.2492A>C and c.1079-1083del in NUP107 had been identified as the founder mutations in East Asian[1-3], while c.1772G>T and c.1886A>G in NUP93 might be the founder mutations in Western Europe and Turkish respectively. Nephrotic syndrome was the most common renal manifestation (68/86, 79.1%). Although the renal prognosis was poor that 80.8% (59/73) of them developed end-stage renal disease within the first two decades, the outcome of renal transplantation in NUP nephropathy is better than patients with other steroid-resistant nephrotic syndrome. Focal segmental glomerulosclerosis was the most prevalent renal biopsy pathologic type (56/65, 86.1%). Various extra-renal manifestations were found in 44.8% (26/58) of patients. Neurological involvement was the most common extra-renal presentation (22/26, 84.6%), including microcephaly (13/22, 59.1%), intellectual disability (12/22, 54.5%), and global developmental delay (10/22, 45.5%). Diverse abnormalities of the facial appearance (8/26, 30.8%), short stature (5/26, 19.2%),and contain convergent strabismus (4/26, 15.4%) had also been reported. There are significant differences in extra-renal manifestations between different genomics. Conclusions: The renal manifestation of NUP nephropathy is highly consistent that most patients suffered early-onset SRNS with FSGS. More than half of the patients had extra-renal symptom concomitantly. Asians showed potential susceptibility to NUP nephropathy. Despite the limited reports, some genotype-phenotype correlations have been gradually revealed.

scholarly journals Novel Mutations in NPHS2 Detected in Both Familial and Sporadic Steroid-Resistant Nephrotic Syndrome

2002 ◽  
Vol 13 (2) ◽  
pp. 388-393 ◽  
Author(s):  
Stephanie M. Karle ◽  
Barbara Uetz ◽  
Vera Ronner ◽  
Lisa Glaeser ◽  
Friedhelm Hildebrandt ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Positional Cloning ◽  
Mutational Analysis ◽  
Causative Gene ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Stage Renal Disease ◽  
End Stage

ABSTRACT. Autosomal recessive steroid-resistant nephrotic syndrome (SRINS) belongs to the heterogeneous group of familial nephrotic syndrome and represents a frequent cause of end-stage renal disease in childhood. This kidney disorder is characterized by early onset of proteinuria, progression to end-stage renal disease, and histologic findings of focal segmental glomerulosclerosis, minimal change nephrotic syndrome, or both. A causative gene, NPHS2, has been mapped to chromosome 1q25-q31 and was recently identified by positional cloning. This study reports five novel NPHS2 mutations: A284V, R196P, V290M, IVS4-1G→T, and 460-467insT in 12 (46%) of 26 multiplex families and in 7 (28%) of 25 single patients with the clinical diagnosis of a SRINS. Because NPHS2 mutations were found in nearly 30% of these patients with “sporadic” SRINS, mutational analysis should also be performed in these patients. Besides better classification of the disease entity, identification of NPHS2 mutations may save some of these patients from unnecessary steroid treatment and also permit the prediction of absence of disease recurrence after kidney transplantation.

scholarly journals The importance of genetic study in steroid-resistant nephrotic syndrome

2019 ◽  
Vol 8 (4) ◽  
pp. 271-282 ◽  
Author(s):  
Sepideh Zununi Vahed ◽  
Hakimeh Moghaddas Sani ◽  
Sima Rajabzadeh ◽  
Ziba Nariman-Saleh-Fam ◽  
Mina Hejazian ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Current Knowledge ◽  
Gene Mutations ◽  
Therapeutic Benefit ◽  
Steroid Resistance ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Filtration Barrier ◽  
Stage Renal Disease ◽  
End Stage

Steroid-resistant nephrotic syndrome (SRNS) is a challenging clinical task. It has heterogeneous etiology and extremely variable clinical outcomes and generally progresses to end-stage renal disease (ESRD). Different gene mutations in podocyte’s slit diaphragm, mitochondria, and cytoskeleton proteins, as well as glomerular basement membrane (GBM) have been associated with SRNS. These proteins regulate the function of the glomerular filtration barrier. Advances in genetic approaches and podocytology have led to discover the SRNS-causing genes that lead to a better understanding of the drug resistance. More than 45 genetic mutations have been recognized in the hereditary form of SRNS. This review offers an update on the current knowledge of steroid resistance-causing gene mutations in podocytes. Understanding the specific genes involved in SRNS would guarantee an optimum therapeutic benefit of steroid treatment.

Frasier syndrome diagnosed in a 4-year-old girl

Open Medicine ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. 142-144
Author(s):  
Biljana Miloševic ◽  
Radovan Bogdanović ◽  
Mirjana Kostić ◽  
Vesna Stojanović
Keyword(s):  
End Stage Renal Disease ◽  
Gonadal Dysgenesis ◽  
Frasier Syndrome ◽  
Post Transplantation ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Proliferative Disease ◽  
Stage Renal Disease ◽  
End Stage ◽  
Male Genotype

AbstractThe authors present the case of a girl with Frasier syndrome that was diagnosed at the age of 4 years. At 3.5 years, she was diagnosed a steroid-resistant nephrotic syndrome associated with focal segmental glomerulosclerosis. The girl presented with female phenotype and male genotype (46XY) as well with gonadal dysgenesis. Genetic analysis confirmed the +2T>C mutation in the intron 9 of the WT1 gene. She developed end-stage renal disease at 14 years, culminating in renal transplantation. The liver biopsy revealed a post-transplantation lymph-proliferative disease.

scholarly journals Steroid-resistant idiopathic nephrotic syndrome in children: long-term follow-up and risk factors for end-stage renal disease

2013 ◽  
Vol 35 (3) ◽  
pp. 191-199 ◽  
Author(s):  
Alberto Zagury ◽  
Anne Louise de Oliveira ◽  
Jose Augusto Araujo Montalvão ◽  
Regina Helena Leite Novaes ◽  
Vinicius Martins de Sá ◽  
...  
Keyword(s):  
Risk Factors ◽  
Nephrotic Syndrome ◽  
End Stage Renal Disease ◽  
Idiopathic Nephrotic Syndrome ◽  
Steroid Resistant ◽  
Long Term Follow Up ◽  
Stage Renal Disease ◽  
End Stage

MO1027EFFICACY OF CALCINEURIN INHIBITORS IN CHILDREN WITH MONOGENIC STEROID-RESISTANT NEPHROTIC SYNDROME

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Larisa Prikhodina ◽  
Svetlana Papizh ◽  
Inna Povolotskaya
Keyword(s):  
Nephrotic Syndrome ◽  
Calcineurin Inhibitors ◽  
Compound Heterozygous ◽  
Target Level ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Pathogenic Variants ◽  
Nail Patella Syndrome

Abstract Background and Aims Monogenic causes of steroid-resistant nephrotic syndrome (SRNS) have been reported for up to one-third of children depending on age of the disease onset. Immunosuppressive treatment of genetic SRNS with calcineurin inhibitors (CNIs) is still controversial. The aim of the study was to investigate the efficacy of CNIs with focus on inducing remission and long-term kidney function in children with monogenic SRNS. Method Retrospective analysis of efficacy CNIs in five children (2M/3F) with monogenic SRNS was performed. Kidney biopsy prior CNIs revealed FSGS (n=4) and MCD (n=1). The initial cyclosporine (CsA) dose was 5 mg/kg/24h to keep a target level of 80-150 ng/ml and tacrolimus (TAC) - 0.1 mg/kg/24h to achieve a target level of 5-10 ng/ml. CsA took all 5 patients with subsequent switching to TAC in 2 children due to cosmetic side effects. The median follow-up period was 165.0 (IQR: 59.0; 185.5) months. Next generation sequencing (NGS) was used for identification of pathogenic variants in all patients. Results The median age at onset of monogenic SRNS was 33.0 (IQR: 16.5; 63.0) months. 2/5 (40%) patients presented with acute SRNS, 1/5 (20%) child with infantile NS, 1/5 (20%) - with isolated nephrotic range proteinuria with hypoalbuminemia and 1/5 (20%) - with NS and extrarenal features of Nail-Patella syndrome. NGS identified previously described pathogenic variants in all 5 children, including NPHS2 homozygous c.28dup (p.Glu87Ter) (n=1), NPHS2 compound heterozygous c.868G>A (p.Val290Met) in combination with c.686G>A (p.Arg229Gln) (n=1), LMX1B heterozygous c.788T>G (p.Val263Gly) (n=1), LMX1B heterozygous c.737G>A (p.Arg246Gln) (n=1), and COL4A3 heterozygous c.2962G>A (p.Gly988Arg) variant (n=1). The median time from diagnosis to initiation of CNIs treatment was 72.0 (IQR: 33.0; 93.0) months. CNIs induced complete remission in 2/5 (40%) patients, presented with acute SRNS, including one girl with MCD due to NPHS2 compound heterozygous variants with mutation-dependent pathogenicity of one (p.R229Q) of them and one boy with FSGS due to COL4A3 heterozygous variant (n=1). Partial remission was induced by CNIs in 2/5 (40%) girls with FSGS due to LMX1B heterozygous variants with isolated SRNS (n=1) and Nail-Patella syndrome (n=1). The median duration of CNIs treatment to obtain complete or partial remission was 13.5 (IQR: 6.8; 15.8) months. Acute CNIs-associated nephrotoxicity had 2 patients with LMX1B variants. At the last follow up full and partial responders to CNIs treatment aged of 16.5 (IQR: 11.8; 17.5) years had CKD-1 (n=3) and CKD-2 (n=1). 1/5 (20%) boy with NPHS2-associated infantile NS was CNI resistant and developed CKD-5 at the age of 6.5 years with subsequent living related kidney transplantation. Conclusion We found that 4/5 (80%) children with monogenic SRNS demonstrated partial or full response to CNIs treatment with stable long-term kidney function. We assume that CNIs might improve podocyte function by stabilization of their cytoskeleton disrupted in patients with monogenic SRNS.

scholarly journals Choreoathetosis Is a Possible Adverse Event of a Commonly Used Antibiotic

2017 ◽  
Vol 9 (1) ◽  
pp. 81-85 ◽  
Author(s):  
Pornchai Sathirapanya
Keyword(s):  
Adverse Event ◽  
Cerebral Cortex ◽  
Literature Review ◽  
End Stage Renal Disease ◽  
Complete Resolution ◽  
Dosage Adjustment ◽  
Systemic Infection ◽  
Pharmacological Interaction ◽  
Stage Renal Disease ◽  
End Stage

Background: Choreoathetosis (CAS) is attributed to a few neuropsychiatric drugs; however, it is scarcely reported with commonly used antibiotics. Aims: To present a case of ceftriaxone (CTX)-induced CAS and to perform a literature review. Setting: A medical teaching hospital. Case History: An 83-year-old female with end stage renal disease was prescribed CTX 2 g/day intravenously and doxycycline (DXC) 200 mg/day orally for the treatment of acute community-acquired systemic infection. CAS developed 3 days after the administration of both drugs. Withdrawal of CTX and DXC yielded complete resolution of the CAS on the following day. Neither neurological adverse events related to DXC use nor pharmacological interaction between DXC and CTX was reported. Therefore, the CAS development was attributed to CTX. Conclusion: CTX as well as other ß-lactam antibiotics induce glutamate excess in the striatum and cerebral cortex, resulting in neurological hyperexcitability disorders. Dosage adjustment of these antibiotics in relation to the patients’ renal clearance is warranted.

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