Approximately one third of children with steroid-resistant nephrotic syndrome (SRNS) carry pathogenic variants in one of the many associated genes. The WT1 gene coding for the WT1 transcription factor is among the most frequently affected genes. Cases from the Czech national SRNS database were sequenced for exons 8 and 9 of the WT1 gene. Eight distinct exonic WT1 variants in nine children were found. Three children presented with isolated SRNS, while the other six manifested with additional features. To analyze the impact of WT1 genetic variants, wild type and mutant WT1 proteins were prepared and the DNA-binding affinity of these proteins to the target EGR1 sequence was measured by microscale thermophoresis. Three WT1 mutants showed significantly decreased DNA-binding affinity (p.Arg439Pro, p.His450Arg and p.Arg463Ter), another three mutants showed significantly increased binding affinity (p.Gln447Pro, p.Asp469Asn and p.His474Arg), and the two remaining mutants (p.Cys433Tyr and p.Arg467Trp) showed no change of DNA-binding affinity. The protein products of WT1 pathogenic variants had variable DNA-binding affinity, and no clear correlation with the clinical symptoms of the patients. Further research is needed to clarify the mechanisms of action of the distinct WT1 mutants; this could potentially lead to individualized treatment of a so far unfavourable disease.

• MeSH
• dítě MeSH
• DNA terapeutické užití   MeSH
• léková rezistence MeSH
• lidé MeSH
• mutace MeSH
• nefrotický syndrom * farmakoterapie   genetika   metabolismus   MeSH
• proteiny WT1 * genetika   metabolismus   MeSH
• steroidy farmakologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA MeSH
• proteiny WT1 * MeSH
• steroidy MeSH
• WT1 protein, human MeSH Prohlížeč

PURPOSE: The aim of our retrospective study was to clarify fertility, pregnancy complications and outcomes in common variable immunodeficiency (CVID) females. METHODS: Retrospective data were obtained from three Czech referral centres. The data were compared with data obtained from the Czech National Registry of Reproduction Health. RESULTS: Our cohort of patients comprised 54 women with 115 pregnancies; 88 pregnancies in 50 females were finished with live births (77 %). In only 8 women (15%) was the diagnosis of CVID established before the first pregnancy. Replacement immunoglobulin therapy was performed in 10 patients without any moderate or severe adverse effects. Compared with the Czech population, the CVID patients suffered significantly more frequently from the threat of preterm labour (p < 0.0001), vaginal bleeding (p = 0.0001), eclampsia/preeclampsia (p = 0.009) and a higher number of stillbirths (p < 0.0001). Furthermore, the frequency of babies with low birth weight (less than 2500 g) born to the CVID patients was increased compared with the normal population (p < 0.0001). Serum IgG, IgA and IgM determination was done in 57 children of 50 mothers showing 13 cases of IgA deficiency (23%). There was no significant difference among the non-symptomatic, symptomatic untreated and symptomatic treated females in any of the determined gynaecological complications. The number of unsuccessful pregnancies was higher in the symptomatic untreated women. CONCLUSIONS: Fertility in CVID patients is not decreased, and their pregnancies could be considered more risky compared with those of the general population.

• Klíčová slova
• CVID, fertility, pregnancy, replacement therapy,
• MeSH
• běžná variabilní imunodeficience komplikace   imunologie   MeSH
• děložní krvácení etiologie   MeSH
• dítě MeSH
• dospělí MeSH
• imunoglobulin A genetika   MeSH
• kohortové studie MeSH
• komplikace těhotenství imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předčasná porodní činnost etiologie   MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• těhotenství imunologie   MeSH
• výsledek těhotenství MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• těhotenství imunologie   MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• imunoglobulin A MeSH