Alternative titles; symbols
HGNC Approved Gene Symbol: SALL2
Cytogenetic location: 14q11.2 Genomic coordinates (GRCh38): 14:21,521,080-21,537,121 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 14q11.2 | ?Coloboma, ocular, autosomal recessive | 216820 | Autosomal recessive | 3 |
Using the unusual but characteristic structural features of the zinc finger protein encoded by the region-specific homeotic gene spalt (sal) of Drosophila, Kohlhase et al. (1996) isolated 2 sal-like transcription units, SALL1 (602218) and SALL2. By Northern blot analysis, Kohlhase et al. (1996) showed that the SALL2 gene is expressed in a subset of human tissues, with highest expression in brain, heart, kidney, or pancreas. By in situ hybridization, they found that SALL1 and SALL2 are expressed in different areas of the fetal brain, probably in distinct sets of neurons.
Using RNA in situ hybridization techniques on human embryonic and fetal eyes, Kelberman et al. (2014) detected expression of SALL2 throughout the retina and developing lens vesicle as well as the periocular mesenchyme at 5 weeks of development, the stage at which optic fissure closure starts. Expression was maintained in the developing retina up to 8 weeks; after completion of fissure closure, it was restricted to the inner neuroblastic layer. Reverse transcription PCR analysis of RNA confirmed SALL2 expression in the cornea, lens, and retina at different developmental stages. Kelberman et al. (2014) concluded that SALL2 plays a role in human eye development before, during, and after optic fissure closure.
Kohlhase et al. (1996) demonstrated by fluorescence in situ hybridization that the SALL2 gene maps to chromosome 14q11.1-q12.1.
In a consanguineous Kuwaiti family in which 3 sibs exhibited nonsyndromic ocular coloboma (216820), Kelberman et al. (2014) identified a homozygous nonsense mutation in the SALL2 gene (E29X; 602219.0001) that segregated with disease in the family and was present in heterozygosity in the unaffected first-cousin parents.
Sato et al. (2003) developed Sall2-null mice and found that these animals showed no apparent abnormal phenotype. Unlike the findings with Sall1-null mice, the morphology and gene expression patterns of the mutant kidneys appeared normal. Mice lacking both Sall1 and Sall2 showed kidney phenotypes comparable to those of mice lacking only Sall1, demonstrating the dispensable role of Sall2 in embryonic and kidney development.
Kelberman et al. (2014) generated Sall2-null mice and observed no overt phenotypic abnormalities; however, histologic analysis of the eyes revealed a colobomatous phenotype, with delayed apposition of the optic fissure margins and persistence of an anterior retinal coloboma phenotype after birth. Sall2-deficient embryos displayed correct posterior closure toward the optic nerve head; upon contact of the fissure margins, dissolution of the basal lamina occurred and Pax2 (167409), known to be critical for this process, was expressed normally. In contrast, anterior closure was disrupted, with the fissure margins either failing to meet or misaligning, leading to a retinal lesion. There was no evidence for a small eye phenotype in any of the homozygous Sall2-null mutant eyes at either the embryonic or adult stage.
In 3 affected sibs from a consanguineous Kuwaiti family with nonsyndromic ocular coloboma (216820), Kelberman et al. (2014) identified homozygosity for a c.85G-T transversion in exon 2 of the SALL2 gene, resulting in a glu29-to-ter (E29X) substitution predicted to produce a severely truncated protein lacking 97% of the coding sequence, including 3 clusters of zinc finger motifs known to be essential for DNA-binding activity. The mutation was present in heterozygosity in the unaffected first-cousin parents and was not found in 6,500 exomes from the NHLBI Exome Variant Server database.
Kelberman, D., Islam, L., Lakowski, J., Bacchelli, C., Chanudet, E., Lescai, F., Patel, A., Stupka, E., Buck, A., Wolf, S., Beales, P. L., Jacques, T. S., Bitner-Glindzicz, M., Liasis, A., Lehmann, O. J., Kohlhase, J., Nischal, K. K., Sowden, J. C. Mutation of SALL2 causes recessive ocular coloboma in humans and mice. Hum. Molec. Genet. 23: 2511-2526, 2014. [PubMed: 24412933] [Full Text: https://doi.org/10.1093/hmg/ddt643]
Kohlhase, J., Schuh, R., Dowe, G., Kuhnlein, R. P., Jackle, H., Schroeder, B., Schulz-Schaeffer, W., Kretzschmar, H. A., Kohler, A., Muller, U., Raab-Vetter, M., Burkhardt, E., Engel, W., Stick, R. Isolation, characterization, and organ-specific expression of two novel human zinc finger genes related to the Drosophila gene spalt. Genomics 38: 291-298, 1996. [PubMed: 8975705] [Full Text: https://doi.org/10.1006/geno.1996.0631]
Sato, A., Matsumoto, Y., Koide, U., Kataoka, Y., Yoshida, N., Yokota, T., Asashima, M., Nishinakamura, R. Zinc finger protein Sall2 is not essential for embryonic and kidney development. Molec. Cell. Biol. 23: 62-69, 2003. [PubMed: 12482961] [Full Text: https://doi.org/10.1128/MCB.23.1.62-69.2003]