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Abstract Background In steroid-resistant nephrotic syndrome (SRNS), protracted proteinuria leads to the loss of thyroxine-binding proteins resulting in low thyroid hormones and in damage renal tubules and exhausts the thyroid reserve. This study aimed to assess thyroid function in those patients with SRNS and steroid-sensitive nephrotic syndrome (SSNS). A comparative cross-sectional study evaluated the thyroid status of 50 children with an equal age- and sex-matched SSNS, and controls were enrolled in this study. Demographic data, clinical examination, renal profile, and thyroid function tests were conducted for them. Results Subclinical non-autoimmune hypothyroidism was significantly prevalent in 54% of SRNS patients and 12% of SSNS patients (p

Abstract Background Familial hypercholesterolemia (MIM: PS143890) is a genetic disorder characterized by an increase in blood cholesterol. LDLR is one of the genes which their defect contributes to the disorder. Affected individuals may carry a heterozygous variant or homozygous/compound heterozygous variants and those with biallelic pathogenic variants present more severe symptoms. Method We report an Egyptian family with familial hypercholesterolemia. Both the proband and parents have the disorder while a sibling is unaffected. Exome sequencing was performed to identify the causal variant. Results LINE‐1 insertion in exon 7 of LDLR was identified. Both parents have a heterozygous variant while the proband has a homozygous variant. The unaffected sibling did not carry the variant. Discussion This insertion may contribute to the high prevalence of hypercholesterolemia in Egypt and the finding underscores the importance of implementing mobile element insertion caller in routine bioinformatics pipeline.

Dominant KCNQ1 variants are well-known for underlying cardiac arrhythmia syndromes. The two heterozygous KCNQ1 missense variants, R116L and P369L, cause an allelic disorder characterized by pituitary hormone deficiency and maternally inherited gingival fibromatosis. Increased K+ conductance upon co-expression of KCNQ1 mutant channels with the beta subunit KCNE2 is suggested to underlie the phenotype; however, the reason for KCNQ1-KCNE2 (Q1E2) channel gain-of-function is unknown. We aimed to discover the genetic defect in a single individual and three family members with gingival overgrowth and identified the KCNQ1 variants P369L and V185M, respectively. Patch-clamp experiments demonstrated increased constitutive K+ conductance of V185M-Q1E2 channels, confirming the pathogenicity of the novel variant. To gain insight into the pathomechanism, we examined all three disease-causing KCNQ1 mutants. Manipulation of the intracellular Ca2+ concentration prior to and during whole-cell recordings identified an impaired Ca2+ sensitivity of the mutant KCNQ1 channels. With low Ca2+, wild-type KCNQ1 currents were efficiently reduced and exhibited a pre-pulse-dependent cross-over of current traces and a high-voltage-activated component. These features were absent in mutant KCNQ1 channels and in wild-type channels co-expressed with calmodulin and exposed to high intracellular Ca2+. Moreover, co-expression of calmodulin with wild-type Q1E2 channels and loading the cells with high Ca2+ drastically increased Q1E2 current amplitudes, suggesting that KCNE2 normally limits the resting Q1E2 conductance by an increased demand for calcified calmodulin to achieve effective channel opening. Our data link impaired Ca2+ sensitivity of the KCNQ1 mutants R116L, V185M and P369L to Q1E2 gain-of-function that is associated with a particular KCNQ1 channelopathy.

Background: Low bone mineral density (BMD) is a characteristic feature of Beta thalassemia major (βTM) patients. Vitamin D is important for bone mineralization. Vitamin D receptors (VDR) genetic variants may be related to vitamin D status and BMD. Objectives: To evaluate the effect of VDR genetic variants on vitamin D levels and BMD in βTM Egyptian patients supplemented with vitamin D. Methods: This study was conducted on forty children with βTM and forty unrelated healthy sex and age-matched controls. Serum calcium, phosphorus, ALP, ferritin and vitamin D were measured. VDR genetic variants (BsmI, TaqI, and FokI) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). BMD was measured by dual-energy X-ray densitometry (DEXA) of the lumbar spine. Results: In βTM patients, 22.5% had deficient, 50% had insufficient and only 27.5% had sufficient levels of vitamin D. BMD Z score was significantly lower in βTM patients compared to controls (p