Anti-ZIC1 (aa 2-95) polyclonal antibody

We report clinical and radiological features of a patient born with an isolated skull malformation of caput membranaceum and partial bicoronal craniosynostosis with a novel, de novo heterozygous missense variant inZIC1[NM_003412.3:c.1183C>G, p.(Pro395Ala)]. Caput membranaceum, or boneless skull, is a rare manifestation of skull ossification defect. It can result from an isolated, enlarged parietal foramina or it can present as part of skeletal dysplasia syndromes associated with poor mineralization such as hypophosphatasia, osteogenesis imperfecta type II, and Saethre-Chotzen syndrome. Their causative genes are well described.ZIC1, Zinc Finger protein of the cerebellum 1 (OMIM #600470) belongs to ZIC family genes, each encoding a Cys2 His2-type zinc finger domain-containing transcription factors. Recent studies have shown that pathogenic variants inZIC1have deleterious effect in developing human central nerves system and skull bone.ZIC1related clinical conditions are reported and include cerebellum malformation, Dandy-Walker malformation, spinal dysraphism, microcephaly, and craniosynostosis with associated intellectual disability. To-date, there is no report of pathogenic variant inZIC1causing isolated caput membranaceum. Our observation adds to the clinical spectrum ofZIC1related skull malformation.

Double anal fin (Da) is a spontaneous medaka mutant that exhibits an unique ventralizing phenotype, a mirror-image duplication across the lateral midline in the dorsal trunk-tail region. In the mutant, early D-V specification appears normal but the altered phenotype becomes evident during late embryogenesis. In this stud, we genetically specified the mutation to a 174-kb region harboring two zinc-finger type transcription factors, zic1 and zic4, and compared the genomic structures of this region between wild-type and Da mutant fish. No mutation was found in the coding regions of either gene of the mutant, while two fragments, 324 bp and 3-4 kb long, were found inserted downstream Of zic1 and zic4, respectively. Probably as a result of this, the expression of both genes is lost in the derivatives of the dorsal (epaxial) somite and the region dorsal to the terminal axis bending. All these tissues are morphologically affected or become ventralized in the mutants. In contrast, the expression in the head region and dorsal spinal cord remained unchanged. Detailed characterization of Da phenotypes revealed a novel defect in the axial skeleton (spina bifida occulta) that was also found in zic1-deficient mice. Finally, zic1-morpholino injection partially phenocopied early Da phenotypes. These findings strongly suggest that zic1 and/or zic4 are required for dorsal identity in the trunk-tail region and that loss of their expression in the epaxial somite derivatives and tail region causes the Da phenotypes. (C) 2004 Elsevier Ireland Ltd. All rights reserved.