Genetic Study of Nephrotic Syndrome in Iranian Children- Systematic Review

Idiopathic nephrotic syndrome is a heterogeneous disease with a spectrum of age at presentation, phenotype, renal pathology, and response to treatment. Many mutations are recognized to be implicated in sporadic or hereditary forms. The aim of this review was to summarize the results of the genetic studies which have already been carried out in Iran considering their limitations.A literature search was conducted from March 1970 to September 2015 through MEDLINE, EMBASE, Google Scholar, Google, Iran Medex, Magiran, and SID. Eleven studies were relevant. Three articles were excluded due to insufficient data, duplicated case, and a syndromic nephrotic case without genetic studies. Our results showed that in the southwest of Iran, 80% of the patients had mutations in NPHS1 while in Fars Province, one third showed mutations in NPHS2 when all exons were assessed. In two different studies conducted in one center in Tehran, no mutation was detected in exon 5 but when all exons were studied, more than 65% had hot spot mutation in exon 8 of NPHS2. Interestingly, none of adolescents with FSGS showed mutation in p.R229Q (NPHS2, exon 5). This review revealed that both NPHS1 and NPHS2 were prevalent in Iranian children with SRNS. No mutation of p.R229Q was reported in Iranian adolescent with SRNS.Keywords: Nephrin; NPHS2 protein; Nephrotic Syndrome; Glomerulosclerosis; Focal Segmental

Fréquence des néphropathies congénitales au Centre hospitalier universitaire de Donka à Conakry: Frequency of congenital nephropathies in the University Hospital of Donka in Conakry

Context and objective. The real extent of congenital nephropathies is little known in Africa and in particular in Guinea. The objective of this study was to determine the prevalence of congenital nephropathies in the University Hospital of Donka. Methods. This was a descriptive retrospective study enrolling patients admitted for congenital nephropathy at both pediatric and pediatric surgery departments of Donka, between January 1st, 2007 and June 30th, 2012. The parameters of the study were epidemiological, clinical and paraclinical data.  Results. Of 34,448 patients recorded during the period studied, 26 had congenital nephropathies. They encompassed nephroblastoma (n=17), SJPU (n=6), hydronephrosis on left multikystic kidney (n=1), multikystic kidney in ptosis (n=1) and renal ectopia (n=1). Male sex was preponderant (21/26) with a sex ratio of 4.2/1. The 29 day-old to 2 year-old children were more affected. Conclusion. Congenital nephropathies appear less frequently in this hospital probably due to the absence of optimal facilities. The early diagnosis of congenital nephropathies should be made during the antenatal time, which would be a key to a better management of these conditions in affected children. Contexte et objectif. L’ampleur réelle des néphropathies congénitales est peu connue en Afrique et notamment en Guinée. L’objectif de cette étude était de déterminer la fréquence des néphropathies congénitales rencontrées. Méthodes. Cette étude documentaire de type descriptif sur la néphropathie congénitale, a été conduite entre les 1er janvier 2007 et 30 juin 2012, dans les services de pédiatrie et de chirurgie pédiatrique de Donka. Les paramètres d’interet englobaient les données épidémiologiques, cliniques et paracliniques.  Résultats. Parmi les 34.448 dossiers colligés, 26 présentaient une néphropathie congénitale. Il s’agissait des néphroblastomes (n=17), des syndromes de jonction pyélo-urétérale (n=6), d’une hydronéphrose sur rein multikystique gauche (n=1), d’un rein multikystique en ptose (n=1) et d’une ectopie rénale (n=1). Le sexe masculin était prépondérant (21/26) avec un sexe ratio de 4,2/1. Les enfants de 29 jours à 2 ans étaient les plus touchés. Conclusion. Les néphropathies congénitales sont paraissent moins fréquentes dans cette institution hospitalière, à cause du manque d’un plateau technique diagnostique optimal. Le diagnostic précoce des néphropathies congénitales devrait être fait dans la période prénatale ce qui permettrait une meilleure prise en charge des enfants affectés

CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population

Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective : This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene . Methods : Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS , followed by direct sequencing of the coding exons of CTNS . Results : From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22; 45.5%), and other five were compound heterozygous for this variant (15/22; 68.2%). The other mutations found were p.Q128X (c.721 C>T; 2/22), p.S139F (c.755 C>T; 4/22) and c.18-21delGACT (p.T7FfsX7; 1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.info:eu-repo/semantics/publishedVersio

Beauty and the (Chemical) Beast

Cosmetics and personal care products (PCPs) are prominent in the daily lives of consumers. Unfortunately, there is a long history of toxic chemicals in these products that have caused serious adverse effects. As a result, the Food, Drug and Cosmetic Act (FD&C) was created to help identify ingredients with safety concerns; this remains the primary source of regulation for cosmetics and PCPs today. No additional requirement exists for federal review of ingredients or adverse event reporting. As a result, questionable ingredients with potential safety issues can still be found in products. With these regulatory deficits, some companies have taken steps to remove unsafe chemicals from their products and promote ‘cleaner’ ones. In addition, resources are available such as the Skin Keep Cosmetics Database, that review ingredients and classify their hazard risk. Knowing the limited regulation of cosmetic and PCPs, it is important for consumers to be knowledgeable about ingredients that may be unsafe or carry risks

NGAL as an early biomarker of kidney disease in Joubert syndrome: three brothers compared.

Joubert syndrome (JBTS) is a rare autosomal recessive disorder with an underestimated prevalence due to lack of recognition of clinical signs or failure to diagnose this pathology. JBTS is clinically heterogeneous, and it is characterized by a multiple organ involvement predominantly due to the requirement for Joubert gene function in several tissues. Renal disease affects approximately 30% of patients with JBTS, presenting itself in most cases as nephronophthisis (NPHP), a structural tubulo-interstitial disorder characterized by thickened basal membrane of the tubular epithelium and progressive interstitial fibrosis, associated with cysts at the cortico-medullary junction. We propose three cases concerning three patients with JBTS having different years of illness and degrees of renal impairment, evaluating the parameters of renal function at the time of genetic diagnosis and seen after a follow-up of 7 years. We measured neutrophil gelatinase-associated lipocalin (NGAL), considered as an excellent predictor of kidney injury, to evaluate whether this biomarker might be an early biomarker for JBTS-related kidney disease. NGAL was high in all three cases, but with different levels, indicating a tubular suffering typical of this syndrome, with dissimilar severity in the analyzed subjects. NGAL could represent an early indicator of renal damage useful to start an intensive nephrologic follow-up