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  • 总部: 泰国曼谷市巴吞汪区仑披尼分区 普勒吉路齐隆巷5号.
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Alternative titles; symbolsZNF925HGNC Approved Gene Symbol: ZBTB42Cytogenetic location: 14q32.33 Genomic coordinates (GRCh38): 14:104,800,553-104,804,711 (fr...

Alternative titles; symbols

  • ZNF925

HGNC Approved Gene Symbol: ZBTB42

Cytogenetic location: 14q32.33 Genomic coordinates (GRCh38): 14:104,800,553-104,804,711 (from NCBI)

▼ Cloning and Expression
Using RT-PCR, Devaney et al. (2011) cloned human ZBTB42 from skeletal muscle RNA. The deduced protein has a calculated molecular mass of about 47 kD and contains an N-terminal POZ domain and 4 C-terminal C2H2-type zinc fingers. Database analysis revealed ZBTB42 orthologs in several vertebrate species. Mouse and human ZBTB42 share 75% amino acid identity. Western blot analysis detected ZBTB42 proteins with apparent molecular masses of 47 and 36 kD in human skeletal muscle. In mouse, the 47-kD protein was highly expressed in skeletal muscle and ovary, with lower expression in brain, lung, spleen, liver, and heart, and no expression in kidney or intestine. The 36-kD protein was highly expressed in mouse skeletal muscle and liver, but was not detected in other tissues. Immunohistochemical analysis of human skeletal muscle showed that ZBTB42 localized to nuclei of myofibers and interstitial connective tissue cells. Confocal microscopy of mouse skeletal muscle localized Zbtb42 within the nucleoplasm of myofiber nuclei, and Zbtb42 was highly enriched in subsynaptic nuclei at the neuromuscular junction.

▼ Gene Structure
Devaney et al. (2011) determined that the ZBTB42 gene contains 2 exons.

▼ Mapping
Hartz (2011) mapped the ZBTB42 gene to chromosome 14q32.33 based on an alignment of the ZBTB42 sequence (GenBank AK125003) with the genomic sequence (GRCh37).

▼ Molecular Genetics
In a consanguineous Saudi Arabian family in which 3 sibs had lethal congenital contracture syndrome (LCCS6; 616248), Patel et al. (2014) excluded linkage to known LCCS loci and identified homozygosity for a missense mutation in the ZBTB42 gene (R397H; 613915.0001) that segregated with disease in the family. The mutation was not found in ethnically matched controls or public databases.

▼ Animal Model
Patel et al. (2014) generated zbtb42-knockdown morphant zebrafish and observed that the morphants were leaner and smaller than controls, with a dorsal curvature reminiscent of that seen in other zebrafish models of myopathy. The morphant zebrafish also exhibited mild bradycardia, and skeletal muscles showed highly reduced birefringence in comparison to controls, suggesting a defect in myofiber organization in somites. In addition, the zbtb42 morphants had decreased spontaneous coiling and diminished touch-evoked escape behaviors, indicative of reduced muscle function and overall muscle weakness. Histologic examination of morphant skeletal muscle revealed disorganized myofibers with fewer myofibers in somites, as well as large areas that completely lacked sarcomeric organization. Whole-mount immunostaining demonstrated that zbtb42 morphants had thinner myofibers than controls, with large gaps between adjacent myofibers; the myofibers also showed areas that lacked myofibrillar striations and appeared to contain aggregates of sarcomeric proteins. Immunofluorescence analysis showed fewer and fragmented neuromuscular junctions (NMJs) compared to the densely branching NMJs seen in controls. Transmission electron microscopy showed significant myofibrillar disarray that lacked normal actin-myosin organization; specifically, zbtb42 morphant skeletal muscle did not have the clearly defined H-zone that is present in wildtype muscles. This knockdown muscle phenotype was successfully rescued with overexpression of wildtype human ZBTB42, but not with the LCCS-associated R397H mutant (613915.0001).

▼ ALLELIC VARIANTS ( 1 Selected Example):

In a stillborn female infant with lethal congenital contracture syndrome (LCCS6; 616248), born of first-cousin Saudi Arabian parents, Patel et al. (2014) identified homozygosity for a c.1190G-A transition in exon 2 of the ZBTB42 gene, resulting in an arg397-to-his (R397H) substitution at a highly conserved residue in the fourth zinc finger-binding domain. The mutation was present in heterozygosity in her unaffected parents and 2 unaffected sibs, whereas 3 other healthy sibs did not carry the mutation; DNA was unavailable from 2 previous stillborn sibs with LCCS. The mutation was not found in 300 Saudi controls, in 485 Saudi exomes, or in the 1000 Genomes Project or Exome Variant Server databases. Zebrafish with zbtb42 knockdown exhibited a severe muscular phenotype that was rescued with overexpression of wildtype human ZBTB42, but not with the R397H mutant.

Tags: 14q32.33