Association of PKD2 (Polycystin 2) Mutations With Left-Right Laterality Defects

作者：Bataille Stanislas; Demoulin Nathalie; Devuyst Olivier; Audrezet Marie Pierre; Dahan Karin; Godin Michel; Fontes Michel; Pirson Yves; Burtey Stephane^*

来源：American Journal of Kidney Diseases, 2011, 58(3): 456-460.

DOI：10.1053/j.ajkd.2011.05.015

• Autosomal dominant polycystic kidney disease
• heterotaxia
• situs inversus
• Pkd2-null mouse

Mutations in the PKD1 (polycystin 1) and PKD2 (polycystin 2) genes cause autosomal dominant polycystic kidney disease (ADPKD). Most Pkd2-null mouse embryos present with left-right laterality defects. For the first time, we report the association of ADPKD resulting from a mutation in PKD2 and left-right asymmetry defects. PKD1 and PKD2 were screened for mutations or large genomic rearrangements in 3 unrelated patients with ADPKD presenting with laterality defects: dextrocardia in one and situs inversus totalis in 2 others. A large gene deletion, a single-exon duplication, and an in-frame duplication respectively, were found in the 3 patients. These polymorphisms were found in all tested relatives with ADPKD, but were absent in unaffected related individuals. No left-right anomalies were found in other members of the 3 families. A possible association between heterotaxia and a PKD2 mutation in our 3 patients is suggested by: (1) the existence of laterality defects in Pkd2-null mouse and zebrafish models and (2) detection of a pathogenic PKD2 mutation in the 3 probands, although PKD2 mutations account for only 15% of ADPKD families. The presence of left-right laterality defects should be systematically screened in larger cohorts of patients with ADPKD harboring PKD2 mutations. Am J Kidney Dis. 58(3): 456-460.

• 出版日期2011-9