Renal and urinary tract disorders

Gene: DZIP1L

Comment on list classification: Gene added by expert reviewer and rated green. PMID: 28530676 - homozygous missense variants reported in 3 families (5 probands), and loss of funtion variants in two additional unrelated patients with ARPKD. Parental consanguinity applied to all cases. A mouse mutant (wpy) with widespread embryonic dysmorphologies, had eight homozygous mutations including a nonsense mutation in the region encoding the coiled-coil domains of Dzip1l (c.1123C>T (p.Gln375*). Histological analysis of kidney sections after at least four crosses to CD1 revealed a highly penetrant progressive cystic-kidney phenotype in Dzip1l wpy/wpy mice. Additional functional evidence was reported, suggesting that the ciliary-membrane translocation of the PKD1 amd PKD2 (both green genes on this panel) is compromised in DZIP1L-mutant cells.

Created: 9 Nov 2017, 12:05 p.m.

Green List (high evidence)

This is a novel cause of recessive cystic kidney disease that mimics ARPKD

Created: 3 Nov 2017, 9:29 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
ARPKD

Publications

• Lu H, Galeano MCR, Ott E, Kaeslin G, Kausalya PJ, Kramer C, Ortiz-Brüchle N, Hilger N, Metzis V, Hiersche M, Tay SY, Tunningley R, Vij S, Courtney AD, Whittle B, Wühl E, Vester U, Hartleben B, Neuber S, Frank V, Little MH, Epting D, Papathanasiou P, Perkins AC, Wright GD, Hunziker W, Gee HY, Otto EA, Zerres K, Hildebrandt F, Roy S, Wicking C, Bergmann C. Mutations in DZIP1L, which encodes a ciliary-transition-zone protein, cause autosomal recessive polycystic kidney disease. Nat Genet. 2017 Jul
• 49(7):1025-1034. doi: 10.1038/ng.3871. Epub 2017 May 22. PubMed PMID: 28530676.

Mode of pathogenicity
Other