ABSTRACT
OBJECTIVE@#To explore the genetic basis for a child with clinically suspected nephronophthisis (NPHP).@*METHODS@#Peripheral blood samples of the patient and her parents were collected subjected to high-throughput sequencing. Sanger sequencing was used to verify the gene variants.@*RESULTS@#The patient, a 7-year-old girl with congenital blindness, was admitted to a local hospital due to repeated vomiting for 7-8 days and then transferred to author's hospital due to renal failure. Her urine occult bloods (3+) and urine protein (1+) were abnormal. Her blood urea nitrogen and creatinine showed a significant progressive increase. Renal ultrasound showed a mild enlargement in bilateral renal, increased echogenicity, loss of corticomedullary differentiation, and the presence of cysts in both kidneys. No familial genetic history was found in the family of patient and the child was clinically diagnosed with nephronophthisis. The proband was found to harbor compound heterozygous variants of the CEP290 gene, namely c.2587-2A>T and c.2251C>T, which were inherited from her mother and father, respectively. Based on the ACMG guidelines, both variants were predicted to be pathogenic.@*CONCLUSION@#The patient was diagnosed with NPHP type 6 due to variants of the CEP290 gene. Above finding has provided new evidence for the genotype-phenotype correlation of this disease.
ABSTRACT
Alterations in the balance between synthesis and degradation of extracellular matrix( ECM) and its remodeling may result in an accumulation of ECM molecules and lead to tubulointerstitial fibrosis and glomerulosclerosis and end-stage renal failure. The major physiologic regulators of ECM degradation in the glomerulus are matrix metalloproteinases ( MMP). Tissue inhibitors of metalloproteinase-2 and-1 (TIMP-2 and TIMP-1)are endogenous inhibitors of MMP-2 and MMP-9 respectively. The expression or activity of MMP and TIMP is different in all kinds of kidney diseases or pathophysiological processes. This article reviews the interrelationship of MMP-2, MMP-9, TIMP-1, TIMP-2 and kidney diseases.