摘要Background:Medullary cystic kidney disease (MCKD) is clinically indistinguishable from several other autosomal-dominant renal diseases;thus,molecular genetic testing is needed to establish a definitive diagnosis.A specific type of single cytosine insertion in the variable number tandem repeat (VNTR) of the mucin 1 (MUC1) gene is the only known cause of MCKD 1;however,genetic analysis of this mutation is difficult and not yet offered routinely.To identify the causative mutation/s and establish a definitive diagnosis in a Chinese family with chronic kidney disease,clinical assessments and genetic analysis were performed,including using a modified genotyping method to identify the MUC1-VNTR single cytosine insertion.Methods:Clinical data from three patients in a Chinese family with chronic kidney disease were collected and evaluated.Linkage analysis was used to map the causative locus.Mutation analysis of uromodulin (UMOD) gene was performed using polymerase chain reaction (PCR) and direct sequencing.For MUC1 genotyping,the mutant repeat units were enriched by MwoI restriction,and then were amplified and introduced into pMD-18T vectors.The 192 clones per transformant were picked up and tested by colony PCR and second round of MwoI digestion.Finally,Sanger sequencing was used to confirm the MUC1 mutation.Results:Clinical findings and laboratory results were consistent with a tubulointerstitial lesion.Linkage analysis indicated that the family was compatible with the MCKD1 locus.No mutations were found in UMOD gene.Using the modified MUC1 genotyping method,we detected the MUC1-VNTR single cytosine insertion events in three patients of the family;and mutation-containing clones were 12/192,14/192,and 5/96,respectively,in the three patients.Conclusions:Clinical and genetic findings could support the MCKD1 diagnosis.The modified strategy has been demonstrated to be a practical way to detect MUC1 mutation.