A missense mutation in associated with defective spermatogenesis and male infertility.

Normal function of the C-terminal Eps15 homology domain-containing protein 1 (EHD1) has previously been associated with endocytic vesicle trafficking, shaping of intracellular membranes, and ciliogenesis. We recently identified an autosomal recessive missense mutation c.1192C>T (p.

Estimated pediatric glomerular filtration rate presentation improves the detection rate of kidney impairment in children.

Background: Accurate interpretation of everyday laboratory work is crucial for the early detection of impaired kidney function. Bedside estimation of glomerular filtration rate (eGFR) in children is based on serum creatinine standardized for body mass, most commonly using the revised Schwartz equation using height. This study evaluates how data presentation affects the correct assessment of children's kidney function.

A Founder Mutation in Presents with Tubular Proteinuria and Deafness.

Background: The endocytic reabsorption of proteins in the proximal tubule requires a complex machinery and defects can lead to tubular proteinuria. The precise mechanisms of endocytosis and processing of receptors and cargo are incompletely understood. EHD1 belongs to a family of proteins presumably involved in the scission of intracellular vesicles and in ciliogenesis.

A multidisciplinary nephrogenetic referral clinic for children and adults-diagnostic achievements and insights.

Background: Genetic kidney diseases contribute a significant portion of kidney diseases in children and young adults. Nephrogenetics is a rapidly evolving subspecialty; however, in the clinical setting, increased use of genetic testing poses implementation challenges. Consequently, we established a national nephrogenetics clinic to apply a multidisciplinary model.

Quantification of FAM20A in human milk and identification of calcium metabolism proteins.

Background: FAM20A, a recently discovered protein, is thought to have a fundamental role in inhibiting ectopic calcification. Several studies have demonstrated that variants of FAM20A are causative for the rare autosomal recessive disorder, enamel-renal syndrome (ERS). ERS is characterized by defective mineralization of dental enamel and nephrocalcinosis suggesting that FAM20A is an extracellular matrix protein, dysfunction of which causes calcification of the secretory epithelial tissues.

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis.

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.

Genetic Identification of Two Novel Loci Associated with Steroid-Sensitive Nephrotic Syndrome.

Background: Steroid-sensitive nephrotic syndrome (SSNS), the most common form of nephrotic syndrome in childhood, is considered an autoimmune disease with an established classic HLA association. However, the precise etiology of the disease is unclear. In other autoimmune diseases, the identification of loci outside the classic HLA region by genome-wide association studies (GWAS) has provided critical insights into disease pathogenesis.

Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney Failure.

For many patients with kidney failure, the cause and underlying defect remain unknown. Here, we describe a novel mechanism of a genetic order characterized by renal Fanconi syndrome and kidney failure. We clinically and genetically characterized members of five families with autosomal dominant renal Fanconi syndrome and kidney failure.

Epidemiology of paediatric renal stone disease: a 22-year single centre experience in the UK.

Background: Whilst still rare, the incidence of paediatric stone disease is increasing in developed countries and it is important to evaluate the aetiology. We set up a dedicated renal stone service for children combining medical and surgical expertise in 1993 and now have a large case series of children to investigate the epidemiology.

Methods: A retrospective hospital note review of children presenting with kidney stones during the last 22 years (1993-2015) was conducted.

Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2.

Hyperinsulinemic hypoglycemia (HI) and congenital polycystic kidney disease (PKD) are rare, genetically heterogeneous disorders. The co-occurrence of these disorders (HIPKD) in 17 children from 11 unrelated families suggested an unrecognized genetic disorder. Whole-genome linkage analysis in five informative families identified a single significant locus on chromosome 16p13.

KCNJ10 mutations display differential sensitivity to heteromerisation with KCNJ16.

Background/aims: Mutations in the inwardly-rectifying K(+)-channel KCNJ10/Kir4.1 cause autosomal recessive EAST syndrome (epilepsy, ataxia, sensorineural deafness and tubulopathy). KCNJ10 is expressed in the distal convoluted tubule of the kidney, stria vascularis of the inner ear and brain glial cells.

Renal hypodysplasia associates with a WNT4 variant that causes aberrant canonical WNT signaling.

Abnormal differentiation of the renal stem/progenitor pool into kidney tissue can lead to renal hypodysplasia (RHD), but the underlying causes of RHD are not well understood. In this multicenter study, we identified 20 Israeli pedigrees with isolated familial, nonsyndromic RHD and screened for mutations in candidate genes involved in kidney development, including PAX2, HNF1B, EYA1, SIX1, SIX2, SALL1, GDNF, WNT4, and WT1. In addition to previously reported RHD-causing genes, we found that two affected brothers were heterozygous for a missense variant in the WNT4 gene.

Nephrocalcinosis (enamel renal syndrome) caused by autosomal recessive FAM20A mutations.

Background/aims: Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood.

Methods: We investigated 25 patients from 16 families with unexplained nephrocalcinosis and characteristic dental defects (amelogenesis imperfecta, gingival hyperplasia, impaired tooth eruption).