ABSTRACT
A 19-year-old female with a learning difficulty, ataxia, and nystagmus was referred to our clinic with advanced chronic kidney disease. Her renal biopsy revealed features of nephronophthisis (NPHP). Magnetic resonance imaging of the brain showed "molar tooth sign." The clinical picture was consistent with Joubert syndrome (JS). Two of her siblings were subsequently found to have a similar condition. Genomic material from the patient, her twin sister, and later on from parents was analyzed for deletion/duplication mutations in the NPHP1 gene using multiplex ligation-dependent probe amplification. No genetic defect was discerned. However, applying the emerging "Next-Generation Sequencing (NGS)" method, we identified a novel c.5704G>T mutation in exon 41 of the CEP290 gene on chromosome 12q21. The identification of this novel mutation, that is, highly likely to be pathogenic was compatible with the diagnosis of JS. This mutation may be included in screening and diagnostic panel. NGS provides an excellent screening method for genetic testing.
Subject(s)
Abnormalities, Multiple/genetics , Antigens, Neoplasm/genetics , Cell Cycle Proteins/genetics , Cerebellum/abnormalities , Cytoskeletal Proteins/genetics , DNA Mutational Analysis/methods , Eye Abnormalities/genetics , High-Throughput Nucleotide Sequencing , Kidney Diseases, Cystic/genetics , Mutation , Retina/abnormalities , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/therapy , Eye Abnormalities/diagnosis , Eye Abnormalities/therapy , Female , Genetic Predisposition to Disease , Heterozygote , Humans , Kidney Diseases, Cystic/diagnosis , Kidney Diseases, Cystic/therapy , Phenotype , Predictive Value of Tests , Prognosis , Risk Factors , Saudi Arabia , Young AdultABSTRACT
Cholesterol crystal emboli (CCE) syndrome involving native kidneys is an underdiagnosed condition. CCE is rare in renal allografts. It may present with acute kidney injury, but usually not acute graft loss. CCE should be considered in patients with a history of atherosclerosis and an invasive arterial procedure who present with acute or chronic renal allograft dysfunction. Therapy for CCE is mainly supportive and carries a high rate of mortality. To the best of our knowledge, this is the first reported case of a patient who lost his native kidneys and renal allograft due to CCE arising from his own vasculature.
