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Item does not contain fulltext, BACKGROUND: The pentad of thrombocytopenia, hemolytic anemia, mild renal dysfunction, neurologic signs, and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpura (TTP). TTP usually occurs in adults as an acquired form but a congenital form in children has also been described. In the latter case, the initial presentation is often with neonatal jaundice and thrombocytopenia. The disorder may subsequently take a relapsing course. Deficiency of a recently identified novel metalloprotease, the von Willebrand factor (vWF)-cleaving protease, originating from mutations in the ADAMTS13 gene plays a major role in the development of TTP. METHODS: Blood for DNA analysis was collected from six unrelated TTP families, consisting of nine patients from four different countries, and was screened for mutations in the ADAMTS13 gene. This gene spans 29 exons encompassing approximately 37 kb. Conventional techniques of DNA extraction, polymerase chain reaction (PCR), and direct cycle sequencing were used. RESULTS: Eight novel ADAMTS13 mutations are presented. Half of the total number of mutant ADAMTS13 alleles are amino acid substitutions. The disease-causing mutations are spread over the gene. The pathogenicity of the individual mutations is based upon their predicted effect on the ADAMTS13 protein and segregation in family members. Although most of the patients (seven out of nine) had symptoms during the neonatal period, they were in a remarkably good condition. Only one of the nine patients had a decreased glomerular filtration rate (GFR) with proteinuria and hematuria. Another patient had epileptic seizures. CONCLUSION: We confirm that deficiency of ADAMTS13 is a molecular mechanism responsible for familial TTP. An early diagnosis allows prophylactic treatment with fresh plasma infusions.

Item does not contain fulltext, BACKGROUND: The pentad of thrombocytopenia, hemolytic anemia, mild renal dysfunction, neurologic signs, and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpura (TTP). TTP usually occurs in adults as an acquired form but a congenital form in children has also been described. In the latter case, the initial presentation is often with neonatal jaundice and thrombocytopenia. The disorder may subsequently take a relapsing course. Deficiency of a recently identified novel metalloprotease, the von Willebrand factor (vWF)-cleaving protease, originating from mutations in the ADAMTS13 gene plays a major role in the development of TTP. METHODS: Blood for DNA analysis was collected from six unrelated TTP families, consisting of nine patients from four different countries, and was screened for mutations in the ADAMTS13 gene. This gene spans 29 exons encompassing approximately 37 kb. Conventional techniques of DNA extraction, polymerase chain reaction (PCR), and direct cycle sequencing were used. RESULTS: Eight novel ADAMTS13 mutations are presented. Half of the total number of mutant ADAMTS13 alleles are amino acid substitutions. The disease-causing mutations are spread over the gene. The pathogenicity of the individual mutations is based upon their predicted effect on the ADAMTS13 protein and segregation in family members. Although most of the patients (seven out of nine) had symptoms during the neonatal period, they were in a remarkably good condition. Only one of the nine patients had a decreased glomerular filtration rate (GFR) with proteinuria and hematuria. Another patient had epileptic seizures. CONCLUSION: We confirm that deficiency of ADAMTS13 is a molecular mechanism responsible for familial TTP. An early diagnosis allows prophylactic treatment with fresh plasma infusions.

Item does not contain fulltext, Patients with primary renal glucosuria have normal blood glucose levels, normal oral glucose tolerance test results, and isolated persistant glucosuria. Congenital renal glucosuria is postulated to be attributable to defects in the SGLT2 gene. The Na(+)/glucose cotransporter gene SGLT2 (= SLC5A2) was analyzed in a Turkish patient with congenital isolated renal glucosuria. Genomic DNA was used as a template for amplification by the polymerase chain reaction of each of the 14 exons of the SGLT2 gene. The amplification products were sequenced. DNA sequence analysis revealed a homozygous nonsense mutation in exon 11 of the SGLT2 gene leading to the formation of a truncated cotransporter. Both parents and a younger brother, all three without renal glucosuria, are heterozygous for the nonsense mutation. Our data provide the first direct evidence of an etiologic role for the sodium/glucose cotransporter type 2 in the pathogenesis of renal glucosuria.

Item does not contain fulltext, Patients with primary renal glucosuria have normal blood glucose levels, normal oral glucose tolerance test results, and isolated persistant glucosuria. Congenital renal glucosuria is postulated to be attributable to defects in the SGLT2 gene. The Na(+)/glucose cotransporter gene SGLT2 (= SLC5A2) was analyzed in a Turkish patient with congenital isolated renal glucosuria. Genomic DNA was used as a template for amplification by the polymerase chain reaction of each of the 14 exons of the SGLT2 gene. The amplification products were sequenced. DNA sequence analysis revealed a homozygous nonsense mutation in exon 11 of the SGLT2 gene leading to the formation of a truncated cotransporter. Both parents and a younger brother, all three without renal glucosuria, are heterozygous for the nonsense mutation. Our data provide the first direct evidence of an etiologic role for the sodium/glucose cotransporter type 2 in the pathogenesis of renal glucosuria.

Item does not contain fulltext, Patients with primary renal glucosuria have normal blood glucose levels, normal oral glucose tolerance test results, and isolated persistant glucosuria. Congenital renal glucosuria is postulated to be attributable to defects in the SGLT2 gene. The Na(+)/glucose cotransporter gene SGLT2 (= SLC5A2) was analyzed in a Turkish patient with congenital isolated renal glucosuria. Genomic DNA was used as a template for amplification by the polymerase chain reaction of each of the 14 exons of the SGLT2 gene. The amplification products were sequenced. DNA sequence analysis revealed a homozygous nonsense mutation in exon 11 of the SGLT2 gene leading to the formation of a truncated cotransporter. Both parents and a younger brother, all three without renal glucosuria, are heterozygous for the nonsense mutation. Our data provide the first direct evidence of an etiologic role for the sodium/glucose cotransporter type 2 in the pathogenesis of renal glucosuria.

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