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Homozygous deletion of NPHP1 can lead to isolated nephronophthisis (NPHP) and syndromic disorders. However, the phenotype of scalp tumor and hydroureteronephrosis in NPHP patients with homozygous deletion of NPHP1 has not been reported. Clinical data, laboratory results, and genetic testing of 4 NPHP patients were collected. Examination of their eyes, heart, and urinary tract and of their hepatobiliary, skeletal, and central nervous systems was evaluated. Isolated NPHP was observed in 1 case, and syndromic disorders were observed in the other 3 patients. Their syndromic disorders showed NPHP combined with central nervous system defects, eye involvement, scalp tumor, arachnoid cyst, or hydroureteronephrosis. Large homozygous deletions covering the whole NPHP1 gene locus were identified in all 4 patients. We report a novel phenotype of scalp tumor and hydroureteronephrosis in NPHP patients with homozygous deletion of NPHP1, paving an avenue for further research on NPHP1 -associated deformity in the skin and the urinary system. [ABSTRACT FROM AUTHOR]

A recombinant expression plasmid pYH12, containing the double-mutation glucose isomerase (GIG138PG247D, GI2) coding gene and its natural regulatory sequence, was constructed for site-specific integration in Streptomyces. The resulting plasmid was introduced into Streptomyces lividans TK54 by protoplast transformation and two apramycin-resistance (AmR) transformants, designated GY2 and BY7, respectively, were obtained further based on enzyme assays. These results for polymerase chain reaction (PCR), Dot blot, and recovery of cloned fragments from the transformant chromosome indicated that the GI2 gene was integrated into the S. lividans chromosome by site-specific recombination, and which was further verified by Southern blot. We found that the free form of plasmid pYH12 co-existing with the integrated form was present in S. lividans. SDS-PAGE analysis showed that the GI2 gene was expressed in S. lividans. The intracellular GI2 specific activity was 1.15 U/mg. The stability of integrants demonstrated that the cloned GI2 gene was stably integrated and expressed even in the absence of selective pressure. [ABSTRACT FROM AUTHOR]

Mutations in the WT1 gene can lead to Denys-Drash syndrome or Frasier syndrome and can also cause isolated nephrotic syndrome (NS). Most patients with isolated NS caused by WT1 mutations present as 46, XX phenotypic females. There have been two cases with an onset age younger than 3 years with isolated NS caused by WT1 mutations presenting as 46, XY phenotypic males. We present a 46, XY phenotypic male patient with isolated NS and end-stage renal disease (ESRD) at the age of 6.3 years. He had normal male external genitalia with normal penis length and soft and normal volume of both testes. A mutation, 1051A>G (K351E), in exon 8 of WT1 was identified in the patient. After starting hemodialysis, manifestations of hypertension and renal failure improved, but he died at 6.8 years of age as a result of respiratory failure and heart failure. Our study supports the necessity of searching for mutations in WT1 in 46, XY phenotypic male patients with isolated NS and ESRD. [ABSTRACT FROM AUTHOR]

Mutations in the WT1 gene, leading to Denys-Drash syndrome and Frasier syndrome, can also cause isolated steroid-resistant nephrotic syndrome (ISRNS). Previous studies have reported six pairs of monozygotic twins with WT1 mutations, including one presenting with discordant phenotypes with identical WT1 mutations being of paternal origin and five pairs of monozygotic twins presenting the same phenotype with identical WT1 mutations. In this study, we report on female monozygotic twins showing discordant phenotypes with an identical de novo WT1 mutation, R394W, and presenting incomplete Denys-Drash syndrome and ISRNS. [ABSTRACT FROM PUBLISHER]