scholarly journals Autosomal Recessive Congenital Ichthyosis and Steroid-Resistant Nephrotic Syndrome due to Homozygous Mutation in the ALOX12B gene: A Novel Association with Review of Literature

2020 ◽  
Author(s):  
Lesa Dawman ◽  
Anit Kaur ◽  
Ritambhra Nada ◽  
Soumalya Chakraborty ◽  
Sanjeev Handa ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Autosomal Recessive ◽  
Skin Lesions ◽  
Homozygous Mutation ◽  
Steroid Resistant ◽  
Congenital Ichthyosis ◽  
Autosomal Recessive Congenital Ichthyosis ◽  
Novel Association ◽  
History Of

AbstractNephrotic syndrome (NS) associated with autosomal recessive congenital ichthyosis (ARCI) is a rare association. We describe a 4-year-old boy with steroid-resistant NS (SRNS) who had a history of ichthyotic skin lesions since birth. Renal biopsy revealed focal segmental glomerulosclerosis (tip variant). The skin biopsy was consistent with the findings of ichthyosis. Next-generation sequencing revealed a homozygous pathogenic variant (c.1625_1626del) in the exon 12 of the ALOX12B gene, confirming the diagnosis of ARCI2. The ALOX12B gene belongs to the lipoxygenase family and has a pivotal role in the formation of lipid layers in the epidermis. Leukotrienes have a counter-regulatory effect within the inflamed glomeruli, which influences the vascular tone and glomerular basement membrane permeability, that can be implicated in the pathogenesis of the NS. This child is currently in remission, on tacrolimus and low-dose prednisolone, with emollients and is on regular follow-up. SRNS associated with congenital ichthyosis secondary to a mutation in the ALOX12B gene has never been reported so far. The knowledge regarding this novel association will help the treating physicians in diagnosing this condition early, which will enable proper genetic counseling and prognostication of the disease to the family.

scholarly journals Expanding the clinical phenotype associated with NIPAL4 mutation: Study of a Tunisian consanguineous family with erythrokeratodermia variabilis—Like Autosomal Recessive Congenital Ichthyosis

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258777
Author(s):  
Cherine Charfeddine ◽  
Nadia Laroussi ◽  
Rahma Mkaouar ◽  
Raja Jouini ◽  
Olfa Khayat ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Mutational Analysis ◽  
Clinical Phenotype ◽  
Homozygous Mutation ◽  
Congenital Ichthyosis ◽  
Whole Exome ◽  
Genes Encoding ◽  
Autosomal Recessive Congenital Ichthyosis ◽  
Connexin Genes ◽  
Disorder Of Cornification

Erythrokeratodermia variabilis (EKV) is a rare disorder of cornification usually associated with dominant mutations in the GJB3 and GJB4 genes encoding connexins (Cx)31 and 30.3. Genetic heterogeneity of EKV has already been suggested. We investigated at the clinical and genetic level a consanguineous Tunisian family with 2 sisters presenting an autosomal recessive form of EKV to better characterize this disease. Mutational analysis initially screened the connexin genes and Whole-exome sequencing (WES) was performed to identify the molecular aetiology of the particular EKV phenotype in the proband. Migratory shaped erythematous areas are the initial presenting sign followed by relatively stable hyperkeratotic plaques are the two predominates characteristics in both patients. However, remarkable variability of morphological and dominating features of the disease were observed between patients. In particular, the younger sister (proband) exhibited ichthyosiform-like appearance suggesting Autosomal Recessive Congenital Ichthyosis (ARCI) condition. No causative mutations were detected in the GJB3 and GJB4 genes. WES results revealed a novel missense homozygous mutation in NIPAL4 gene (c.835C>G, p.Pro279Ala) in both patients. This variant is predicted to be likely pathogenic. In addition, in silico analysis of the mutated 3D domain structure predicted that this variant would result in NIPA4 protein destabilization and Mg2+ transport perturbation, pointing out the potential role of NIPAL4 gene in the development and maintenance of the barrier function of the epidermis. Taken togheter, these results expand the clinical phenotype associated with NIPAL4 mutation and reinforce our hypothesis of NIPAL4 as the main candidate gene for the EKV-like ARCI phenotype.

scholarly journals NIPAL4 mutation c.527C˃A identified in Romanian patients with autosomal recessive congenital ichthyosis

2016 ◽  
Vol 24 (4) ◽  
pp. 387-398
Author(s):  
Dalila Maier ◽  
Adrian Florea ◽  
Mariana Cornelia Tilinca ◽  
Ancuța Zazgyva ◽  
Rodica Cosgarea
Keyword(s):  
Autosomal Recessive ◽  
Direct Sequencing ◽  
Case Series ◽  
Skin Condition ◽  
Current Data ◽  
Homozygous Mutation ◽  
Congenital Ichthyosis ◽  
Transglutaminase 1 ◽  
Autosomal Recessive Congenital Ichthyosis

Abstract Introduction: Autosomal recessive congenital ichthyosis is a non-syndromic ichthyosis, with a genetic background of mutations in 9 genes. This case series presents clinical and paraclinical particularities of 3 Romanian ARCI patients with NIPAL4 mutation c.527C>A. Material and methods: Three Caucasian patients were investigated, two sisters and an unrelated female patient, aged 47, 49, and 42 respectively. Skin anomalies were recorded and documented photographically; peripheral blood samples were harvested for DNA extraction and gene analysis. Skin biopsies were used for histological assessment, electron microscopy, and evaluation of in situ transglutaminase 1 activity. Results: All patients presented with generalized ichthyosis, palmoplantar keratoderma, normal hair shafts, and significant oral manifestations. Natural evolution was relatively stable in all cases, without phenotype changing. Medical treatment with retinoids in patients 1 and 2 resulted in normalisation of the skin condition. Histological samples showed hyperkeratosis, acanthosisand perivascular inflammatory infiltrates in the dermis. Positive findings of transglutaminase 1 in situ activity excluded TGM1 deficiency. Direct sequencing of amplicons revealed one homozygous mutation in exon 4, a c.527C>A missense mutation. Conclusions: This is the first report of the hotspot mutation NIPAL4 c.527C>A in Romanian autosomal recessive congenital ichthyosis patients. The phenotype was similar to that reported in the literature, while transglutaminase 1 activity in situ assay detected differences in enzyme distribution between patients bearing the same mutation but different phenotypes. Based on the current data, NIPAL4 mutations are more frequent than TGM1 mutations in Romanian patients with autosomal recessive congenital ichthyosis.

scholarly journals Evaluation of Clinical and Follow-up Results of Patients with Congenital Nephrotic Syndrome

2021 ◽  
pp. 97-100
Author(s):  
Hülya Nalçacıoğlu ◽  
Demet Tekcan ◽  
Hülya Gözde Önal ◽  
Özlem Aydoğ
Keyword(s):  
Nephrotic Syndrome ◽  
Clinical Laboratory ◽  
Congenital Nephrotic Syndrome ◽  
Homozygous Mutation ◽  
Dialysis Treatment ◽  
Filtration Barrier ◽  
Management Of Complications ◽  
Genes Encoding ◽  
History Of

Congenital nephrotic syndrome (CNS) is characterized by severe proteinuria, hypoalbuminemia, and edema within the first three months of life. Congenital nephrotic syndrome can occur due to perinatal infections or mutation of genes encoding structural or regulatory proteins of the glomerular filtration barrier. Treatment includes albumin infusions, nephrectomy, dialysis, and transplantation. In this study, we aimed to evaluate the demographic, clinical, and follow-up results of patients with CNS followed up in our center between 2010 and 2020. Demographic, clinical, laboratory values of 8 patients diagnosed with CNS between 2010 and 2020, kidney biopsy results, genetic examinations, and follow-up results were retrospectively evaluated. A total of 8 patients (4 girls) were included in this study. The median age at diagnosis was 36 days (3 days-8 months) and the follow-up period was 34 months (7-114 months). There was a history of prematurity and consanguinity in 5 patients. Edema was detected at the admission of all patients. Albumin infusion and captopril therapy were started from the diagnosis. No pathology was seen in the tests for perinatal infection, and ultrasonographic examinations were normal. In the genetic analysis, NPHS1 (Nephrin) homozygous mutation was detected in six patients, and coenzyme Q2 mutation was detected in one patient. Peritoneal dialysis treatment was performed in four patients during the follow-up, and unilateral nephrectomy was completed in one patient. During the follow-up, four of eight patients (three due to sepsis while on dialysis, one on the postoperative after the first day of transplantation) died. Three patients are followed up with kidney transplantation and one with supportive treatment. According to our results, most CNS cases are genetic, and nephrin mutation is the most common cause. Management of complications in CNS is crucial for patient surviva

scholarly journals Late-onset nephrotic syndrome with thyroid hypoplasia and nup85 mutation in Galloway-Mowat syndrome: A case report

2021 ◽  
pp. 369-372
Author(s):  
Anirban Sen ◽  
Atanu Pal ◽  
Ankit Ankit ◽  
Koushik Bhattacharjee ◽  
Dipankar Sircar ◽  
...  
Keyword(s):  
Renal Function ◽  
Nephrotic Syndrome ◽  
Autosomal Recessive ◽  
Late Onset ◽  
Cerebellar Atrophy ◽  
Facial Dysmorphism ◽  
Homozygous Mutation ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Intellectual Function

Galloway-Mowat syndrome is an autosomal recessive rare hereditary disorder with progressively worsening renal function, neurological and psychomotor abnormalities, microcephaly, facial dysmorphism, and thyroid, adrenal, and ovarian hypoplasia/agenesis. Here, we present the case of a 9-year-old girl who presented with late-onset steroid-resistant nephrotic syndrome with rapid worsening of renal function, microcephaly, hypertelorism, high-arched palate, delayed speech and developmental milestones, poor intellectual function, short stature, hypertension, and hypothyroidism. Magnetic resonance imaging brain was suggestive of cerebral and cerebellar atrophy, hypomyelination, and optic atrophy. Renal biopsy was suggestive of focal segmental glomerulosclerosis. Whole-genome exon sequencing revealed a homozygous mutation in the NUP85 gene. The clinicians should be aware of this rare syndrome and consider it as a possibility in any patient presenting with nephrotic syndrome, microcephaly, and neurological abnormality.

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 Mutations in Transglutaminase 1 Gene in Autosomal Recessive Congenital Ichthyosis in Egyptian Families

2004 ◽  
Vol 20 (6) ◽  
pp. 325-332 ◽  
Author(s):  
R. M. Shawky ◽  
N.S. Sayed ◽  
N.A. Elhawary
Keyword(s):  
Restriction Endonuclease ◽  
Splice Site ◽  
Autosomal Recessive ◽  
Splice Mutation ◽  
The Other ◽  
Splice Acceptor ◽  
Acceptor Splice Site ◽  
Congenital Ichthyosis ◽  
Transglutaminase 1 ◽  
Autosomal Recessive Congenital Ichthyosis

Autosomal recessive congenital ichthyosis (ARCI) is a rare heterogeneous keratinization disorder of the skin. It is clinically divided into 2 subtypes, lamellar ichthyosis (LI) and congenital ichthyosiformis erythroderma (CIE). We investigated forty-three ARCI Egyptian individuals in 16 severe LI, and 10 CIE families. We identified 5 alleles in two Egyptian families as having intron-5/exon-6 splice acceptor mutation recognized by theMspIrestriction endonuclease. This promoted to a frequency of 9.6% for this mutation (5 splice-mutation alleles/52 alleles tested). We extended our previous dataset to update the detection of R142H mutation in 4 CIE Egyptian families and one LI phenotype (frequency of 28.8%; 15/52), whereas we still had no R141H among our Egyptian population. There was no correlation between phenotype and genotype in our study. Surprisingly, the mutant alleles detected in intron-5 acceptor splice-site were associated with the other extreme of CIE phenotypes rather than the severe LI form. We clearly demonstrated that the ARCI Egyptian families in Upper Egypt was ethnically pure and had a tendency not to be a hybrid with other populations in Lower Egypt, Delta zone and Cairo city.

Coeliac crisis mimicking nephrotic syndrome in a post-partum patient

2019 ◽  
Vol 64 (3) ◽  
pp. 116-118
Author(s):  
Özant Helvacı ◽  
Seyma Yıldız ◽  
Berfu Korucu ◽  
Ulver Derici ◽  
Turgay Arinsoy
Keyword(s):  
Nephrotic Syndrome ◽  
Coeliac Disease ◽  
Post Partum ◽  
Lower Extremity Weakness ◽  
Case Presentation ◽  
Multisystem Involvement ◽  
Life Threatening ◽  
History Of ◽  
Rare Occasion

Background Coeliac crisis is a life-threatening presentation of coeliac disease. Severe diarrhoea, weight loss, electrolyte imbalances and malnutrition are prominent features. Although mainly a disease of childhood, it can on the rare occasion be diagnosed in adults. Case presentation A 25-year-old female with severe generalised oedema, lower extremity weakness, hypokalemia and profound hypoalbuminemia was referred with an initial diagnosis of nephrotic syndrome. Three months previously she had given birth to a healthy child following an uneventful pregnancy. She did not have proteinuria. She had a history of diarrhoea with gluten-containing food since childhood but lacked a formal diagnosis of coeliac disease. A duodenal biopsy confirmed the suspected diagnosis. Coeliac crisis was diagnosed with life-threatening multisystem involvement. Introduction of a gluten-free diet abolished all disease symptoms and ameliorated laboratory parameters at six months’ follow-up. Conclusion Coeliac crisis is a rare, yet dangerous presentation of coeliac disease in adults. As this case suggests, it can present with generalised oedema and hypoalbuminemia mimicking nephrotic syndrome. Rapid diagnosis is the key to successful treatment.

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