ABSTRACT
<p><b>OBJECTIVE</b>To explore the clinical and pathological features and the diagnosis of childhood Alport syndrome (AS).</p><p><b>METHODS</b>A retrospective analysis was performed on clinical data of 91 children with AS.</p><p><b>RESULTS</b>Hematuria was observed in all 91 patients, of whom 86 were accompanied with proteinuria. Sixty-one children with X-Linked AS (XL-AS) had positive family history. Renal biopsy was performed on 82 children. Mild to moderate mesangial proliferation was observed in 74 cases. Small amounts of immune complexes deposits in the glomerular mesangial area were observed in 48 cases. Glomerular basement membrane (GBM) attenuation, thickening and layering were observed in 53 cases by electron microscopy (EM). In 63 cases receiving renal tissue type IV collagen α3 and α5 chain immunofluorescence detection, 58 were diagnosed with AS, including 53 cases of XL-AS and 5 cases of autosomal recessive AS. In 91 cases of AS, 58 were diagnosed as AS by renal tissue type IV collagen α3 and α5 chain immunofluorescence, 21 were diagnosed by EM, one was diagnosed by skin biopsy, and 12 were diagnosed by gene detection. Six novel mutations of COL4A5 gene were found. Forty-five cases were misdiagnosed before the diagnosis of AS. Forty-one of the 45 cases received steroids and/or immunosuppressant therapy.</p><p><b>CONCLUSIONS</b>The clinical manifestations and pathological changes are not specific in children with AS, resulting in a higher rate of misdiagnosis. Typical lesions of GBM under EM are only observed in a part of patients. There is a high novel mutation rate of COL4A5 in the detected AS children.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Male , Collagen Type IV , Genetics , Diagnostic Errors , Glomerular Basement Membrane , Pathology , Nephritis, Hereditary , Diagnosis , Genetics , Pathology , Retrospective StudiesABSTRACT
<p><b>OBJECTIVE</b>To study the clinical and pathological features of Denys-Drash syndrome (DDS).</p><p><b>METHOD</b>Three DDS cases who were treated in our department from December 2009 to June 2011 were subjected to this study by reviewing of literature.</p><p><b>RESULT</b>Both case 1 and case 2 were female, with karyotype 46, XX. Case 3 was male with bilateral cryptorchidism. The ages of nephropathy onset of the three cases were 1 year and 9 months, 2 years and 8 moths, and 3 months respectively. Proteinuria in case 2 and case 3 were evidenced to be resistant to steroid. Case 1 was partially responsive to tacrolimus, plasma albumin and cholesterol were improved, although proteinuria was persistent after Tacrolimus was administered. Remission was achieved in case 2 after administration of cyclosporine A and later tacrolimus, and her renal function remains normal till present (4 years and 9 months). Residue renal histology revealed diffused mesangial sclerosis (DMS) in all three patients. All of the three patients had developed right unilateral Wilms tumor. A novel WT1 missense mutation exon 9 c.1213C > G was detected in case 1. WT1 exon 9 c.1168C > T nonsense mutation and exon 8 c.1130A > T missense mutation were detected in case 2 and case 3, respectively.</p><p><b>CONCLUSION</b>The clinical manifestation of nephropathy in DDS is variable. The majority present with early onset nephropathy and reach renal failure before the age of 4 years. But in a few patients, nephropathy can also be present much later and progress slowly. Proteinuria in DDS is resistant to steroid but is responsive to calcineurin inhibitors, including Cyclosporine A. The effectiveness of tacrolimus was also observed in this study. DDS is evidently caused by WT1 mutation. DMS is the characteristic renal pathological change in DDS.</p>
Subject(s)
Female , Humans , Infant , Male , Cyclosporine , Therapeutic Uses , Denys-Drash Syndrome , Drug Therapy , Genetics , Pathology , Fatal Outcome , Genes, Wilms Tumor , Heterozygote , Mutation , Nephrotic Syndrome , Drug Therapy , Genetics , Pathology , Proteinuria , Drug Therapy , Sclerosis , Drug Therapy , Genetics , Pathology , Tacrolimus , Therapeutic Uses , Treatment Outcome , WT1 Proteins , Genetics , Wilms Tumor , Drug Therapy , Genetics , PathologyABSTRACT
<p><b>OBJECTIVE</b>To identify potential mutations in a Chinese collodion baby.</p><p><b>METHODS</b>The patient was investigated clinically. DNA was extracted from peripheral blood of the baby and his parents. All coding exons(exons 2-15) and splicing sites of transglutaminase 1(TGM1) were amplified by polymerase chain reaction (PCR). Mutation detection was performed by directed sequencing of the PCR products. A total of 100 healthy unrelated subjects were used as controls. Haplotypes were constructed with microsatellites flanking the locus, and TGM1 genotypes of the family were used to determine parental origins of the mutations. CLUSTAL X (1.81) was employed to analyze cross-species conservation of the mutant protein sequence.</p><p><b>RESULTS</b>The boy was found to be a compound heterozygote for two novel mutations: c.420A>G (I140M) from his father and c.832G>A (G278R) from his mother, with the former occurring in the transglutaminase N domain and the latter between transglutaminase N and transglutaminase-like domains. Both mutations were absent from the control subjects.</p><p><b>CONCLUSION</b>The boy's condition was caused by two novel compound heterozygous mutations of c.420A>G and c.832G>A of TGM1. Author's results may provide new clues for molecular diagnosis of this disease.</p>