Heterozygous deletion of the linked genes ZIC1 and ZIC4 is involved in Dandy-Walker malformation.
Dandy-Walker malformation (DWM; OMIM #220200) is a common but poorly understood congenital cerebellar malformation in humans. Through physical mapping of 3q2 interstitial deletions in several individuals with DWM, we defined the first critical region associated with DWM, encompassing two adjacent Zinc finger in cerebellum genes, ZIC1 and ZIC4. Mice with a heterozygous deletion of these two linked genes have a phenotype that closely resembles DWM, providing a mouse model for this malformation.
Grinberg
Inessa
I
Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA.
Northrup
Hope
H
Ardinger
Holly
H
Prasad
Chitra
C
Dobyns
William B
WB
Millen
Kathleen J
KJ
D000818:Animals; D002531:Cerebellum / Q000002:abnormalities; D002648:Child; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D003616:Dandy-Walker Syndrome / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D020161:Physical Chromosome Mapping; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C492123:ZIC1 protein, human; C492799:ZIC4 protein, human; C492122:Zic1 protein, mouse