Clinical Pictures and Novel Mutations ofWT1-Associated Denys–Drash Syndrome in Two Chinese Children

Abstract

Denys-Drash syndrome (DDS) is characterized by early onset of nephropathy, genitalia malformation, and Wilms' tumor, where WT1 is the gene that is mutated in most patients. We report two de novo mutations in WT1 found in two Chinese DDS children. Patient 1 was a boy with complete DDS who was presented with progressive nephropathy, unilateral Wilms' tumor, bilateral cryptorchidism, and renal histology showing diffuse mesangial sclerosis (DMS). When the patient was 24 months old, a liver ultrasound showed multiple nodules, and the patient died of pneumonia 1 month later. The de novo novel mutation, c.1130A>T (p.His377Leu), was identified; the mutation replaces histidine with leucine in the zinc finger (Znf) structure and is predicted to change the local spatial structure of the protein. Patient 2 had 46 XX with incomplete DDS and presented with normal genitalia, proteinuria, unilateral Wilms' tumor with renal pedicle lymph node metastasis, and renal histology showing DMS. Her renal function remains normal after 48 months. A de novo mutation, c.1168C>T (p.Arg390Term), was identified; it truncates 60 amino acids at the C terminus, and it is predicted to result in loss of the DNA-binding capacities of the WT1 protein.

Clinical features and an atypical WT1 mutant site in a child with incomplete Denys-Drash syndrome

“…Incomplete variants present with nephropathy with either intersex disorders or Wilms’ tumor 1. Most DDS patients carry WT1 mutations in exon 8 or 9 1. Here, we report an incomplete DDS child who carried a novel WT1 missense mutation in exon 6 and had unique clinical manifestations.…”

“…Incomplete variants present with nephropathy with either intersex disorders or Wilms’ tumor 1. Most DDS patients carry WT1 mutations in exon 8 or 9 1.…”

“…DDS patients usually present with congenital or early onset proteinuria and progress to end-stage renal disease before 4 years 1. The most common histology of DDS is diffuse mesangial sclerosis; whereas, minimal change disease can also be observed occasionally 6.…”

46,XY-disorder of sex development due to a mutation in the WT1 gene

“…Пробанди з каріотипом 46,ХХ зазвичай мають правильно сформовані зовнішні геніталії за жіночим типом і клінічні прояви синдрому стосуються лише нирок (ізольований нефротичний синдром). Тип успадкування синдрому аутосомно-домінантний [12,[14][15][16].…”

Denys Drash Syndrome Presenting with Renal Failure in the Early Period

“…Bu olguların çoğu 46, XY karyotipinde olup genellikle yenidoğan döneminde ambigus genitalya ile gelirken, 46, XX karyotipli normal dişi genitalya ile gelen olgular da bildirilmiştir. DDS 46, XY karyotipli hastalar Wilms tümörü, psödohermafroditizm ve ilerleyici glomerülopati ile, 46, XX karyotipli hastalar ise Wilms tümörü ve ilerleyici glomerülopati ile seyreder (1)(2) …”