Cystinosis: practical tools for diagnosis and treatment

Cystinosis is the major cause of inherited Fanconi syndrome, and should be suspected in young children with failure to thrive and signs of renal proximal tubular damage. The diagnosis can be missed in infants, because not all signs of renal Fanconi syndrome are present during the first months of life. In older patients cystinosis can mimic idiopathic nephrotic syndrome due to focal and segmental glomerulosclerosis. Measuring elevated white blood cell cystine content is the corner stone for the diagnosis. The diagnosis is confirmed by molecular analysis of the cystinosin gene. Corneal cystine crystals are invariably present in all patients with cystinosis after the age of 1 year. Treatment with the cystine depleting drug cysteamine should be initiated as soon as possible and continued lifelong to prolong renal function survival and protect extra-renal organs. This educational feature provides practical tools for the diagnosis and treatment of cystinosis

Localization of intranuclear RNA by electron microscopy in situ hybridization using a genomic DNA probe

Background: The presence of RNA in the cell nucleus is well known, However, a high resolution in situ hybridization evidence for the presence of RNA in some nuclear pArtículo de investigacións is still lacking, The aim of this work is to localize RNA in subnuclear pArtículo de investigacións using a novel ultrastructural in situ hybridization procedure. In this study, biotinylated genomic mouse DNA as a probe to localize total RNA in the nuclei of mouse hepatocytes was used. Methods: The procedure is based on paraformaldehyde fixation and embedding in lowicryl resin, Thin sections are mounted in formvar-coated gold grids. Hybridization is performed on non-denatured thin sections. DNA-RNA hybrids are detected with streptavidin-10 nm gold pArtículo de investigacións complex. By controlling the time of nick-translation during incorporation of biotin into the probe, labeling in the fibrillar portions of the nucleoplasm is obtained. More digested probes generate more labeling in the granular components. Nucleoli were similarly labeled. Results: As expected, no label was observed in the compact chromatin clumps. These results indicate that granular components as perichromatin granules in the nucleus contain more processed RNA than fibrillar portions, As a comparison, viral DNA sequences on denatured RNase-treated thin sections of adenovirus-2 (Ad-2)-infected human cells were detected. As previously reported, at late stages DNA was observed in the viral pArtículo de investigacións and surrounding nucleoplasm, where Ad-2 DNA is synthesized, Conclusions: The present procedure allows the study of intranuclear RNA distribution and will be useful for the analysis of RNA processing in several types of cells

Further delineation of achondroplasia-hypochondroplasia complex with long-term survival

Achondroplasia-hypochondroplasia (ACH-HCH) complex is caused by the presence of two different pathogenic variants in each allele of FGFR3 gene. Only four patients with confirmed molecular diagnoses have been reported to date, and the phenotype has not been fully defined. Here, we describe a Mexican patient with a confirmed molecular diagnosis of ACH-HCH complex. This patient exhibits intellectual disability, has a history of seizures, experienced multiple cardiorespiratory complications during early childhood, and required foramen magnum decompression. However, he now shows a stable health condition with long-term survival (current age, 18 years). This case is particularly relevant to our understanding of ACH-HCH complex and for the genetic counseling of couples who are affected with ACH or HCH

Genetic basis of cystinosis in Turkish patients: a single-center experience.

Item does not contain fulltextWe report the molecular findings for the CTNS gene in 12 Turkish cystinosis patients aged 7-29 years. All presented initially with severe failure to thrive, polyuria, and polydipsia. Cystinosis was diagnosed at age 1 month to 9 years. Seven patients reached end-stage renal failure at ages ranging from 6.5 to 15 years. Whereas three of the remaining five have renal Fanconi syndrome with proteinuria, two have had kidney failure of varying degrees. Molecular analyses involved an initial multiplex polymerase chain reaction (PCR) to determine the presence or absence of the 57-kb northern European founder deletion in CTNS, followed by sequencing of the ten coding exons of CTNS. Comprehensive mutation analysis verified that none of the 12 patients carried the common 57-kb deletion. We identified four previously reported nucleotide variations associated with cystinosis and five new variants: a 10-kb deletion, three missense variants, and a nucleotide substitution in a potential branch point site of intron 4. This study is the first molecular analysis of Turkish cystinosis patients and provides guidance for the molecular diagnosis of cystinosis in this population.1 januari 201