Autosomal dominant polycystic kidney disease in a family with mosaicism and hypomorphic allele

BMC Nephrology

Vladimír Tesař²  Milada Kohoutová¹  Marie Korabečná¹  Petr Lněnička¹  Veronika Elišáková¹  Jaroslav Kotlas¹  Miroslav Merta¹  Jitka Štekrová¹  Jana Reiterová² 

[1] Department of Nephrology of the 1st Faculty of Medicine and General Teaching Hospital, Charles University, U Nemocnice 2, Prague 2, 128 00, Czech Republic;Institute of Biology and Medical Genetics of the 1st Faculty of Medicine and General Teaching Hospital, Charles University, Albertov 4, Prague 2, 128 00, Czech Republic

关键词: Kidney transplantation;    Mosaicism;    Hypomorphic allele;    PKD2 gene;    PKD1 gene;    Autosomal dominant polycystic kidney disease;   

Others  :  1082979
DOI  :  10.1186/1471-2369-14-59

 received in 2012-10-10, accepted in 2013-02-26,  发布年份 2013

【 摘 要 】

Background

Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of inherited kidney disease that results in renal failure. ADPKD is a systemic disorder with cysts and connective tissue abnormalities involving many organs. ADPKD caused by mutations in PKD1 gene is significantly more severe than the cases caused by PKD2 gene mutations. The large intra-familial variability of ADPKD highlights a role for genetic background.

Case presentation

Here we report a case of ADPKD family initially appearing unlinked to the PKD1 or PKD2 loci and the influence of mosaicism and hypomorphic allele on the variability of the clinical course of the disease. A grandmother with the PKD1 gene mutation in mosaicism (p.Val1105ArgfsX4) and with mild clinical course of ADPKD (end stage renal failure at the age of 77) seemed to have ADPKD because of PKD2 gene mutation. On the other hand, her grandson had a severe clinical course (end stage renal disease at the age of 45) in spite of the early treatment of mild hypertension. There was found by mutational analysis of PKD genes that the severe clinical course was caused by PKD1 gene frameshifting mutation inherited from his father and mildly affected grandmother in combination with inherited hypomorphic PKD1 allele with described missense mutation (p.Thr2250Met) from his clinically healthy mother. The sister with two cysts and with PKD1 hypomorphic allele became the kidney donor to her severely affected brother.

Conclusion

We present the first case of ADPKD with the influence of mosaicism and hypomorphic allele of the PKD1 gene on clinical course of ADPKD in one family. Moreover, this report illustrates the role of molecular genetic testing in assessing young related kidney donors for patients with ADPKD.

【 授权许可】

   
2013 Reiterová et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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