Cystic kidney disease

Gene: DZIP1L

Reviewer Yu Leng Phua adds 3 additional cases from PMID: 35211789 Hertz et al 2022 supporting the existing green rating for this gene.

Created: 29 May 2023, 10:07 p.m. | Last Modified: 29 May 2023, 10:07 p.m.

Panel Version: 4.6

Green List (high evidence)

Four children from three consanguineous families presenting with polycystic kidney disease;
Variants: c.193 T > C; p.(Cys65Arg), and c.216C > G; p.(Cys72Trp);
Functional analyses of the c.216C > G; p.(Cys72Trp) variant indicated mislocalization of mutant DZIP1L;
NOTE: Lack of liver phenotype in these patients

Created: 11 Mar 2022, 1:20 p.m. | Last Modified: 11 Mar 2022, 1:20 p.m.

Panel Version: 2.35

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
# 617610 POLYCYSTIC KIDNEY DISEASE 5; PKD5

Publications

• 35211789

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