1. Function

2. Structure

3. Clinical significance

4. References

5. Further reading

6. External links

Function

With an average worldwide prevalence of 1/800 live births, oral clefts are one of the most common birth defects.^[4] Although over 300 malformation syndromes can include an oral cleft, non-syndromic forms represent about 70% of cases with cleft lip with or without cleft palate (CL/P) and roughly 50% of cases with cleft palate (CP) only. Non-syndromic oral clefts are considered ‘complex’ or ‘multifactorial’ in that both genes and environmental factors contribute to the etiology. Current research suggests that several genes are likely to control risk, as well as environmental factors such as maternal smoking.^[5]

Re-sequencing studies to identify specific mutations suggest several different genes may control risk to oral clefts, and many distinct variants or mutations in apparently causal genes have been found reflecting a high degree of allelic heterogeneity. Although most of these mutations are extremely rare and often show incomplete penetrance (i.e., an unaffected parent or other relative may also carry the mutation), combined they may account for up to 5% of non-syndromic oral cleft.^[5]

Mutations in the SATB2 gene have been found to cause isolated cleft palates.^[6] SATB2 also likely influences brain development. This is consistent with mouse studies that show SATB2 is necessary for proper establishment of cortical neuron connections across the corpus callosum, despite the apparently normal corpus callosum in heterozygous knockout mice.^[7]

Structure

SATB2 is a 733 amino-acid homeodomain-containing human protein with a molecular weight of 82.5 kDa encoded by the SATB2 gene on 2q33. The protein contains two degenerate homeodomain regions known as CUT domains (amino acid 352–437 and 482–560) and a classical homeodomain (amino acid 614–677). There is an extraordinarily high degree of sequence conservation, with only three predicted amino-acid substitutions in the 733 residue protein with I481V, A590T and I730T being amino acid differences between the human and the mouse protein.

Clinical significance

SATB2 has been implicated as causative in the cleft or high palate of individuals with 2q32q33 microdeletion syndrome.^[7]

The role of SATB2 in tooth and jaw development is supported by the identification of a de novo SATB2 mutation in a male with profound mental retardation and jaw and tooth abnormalities and a translocation interrupting SATB2 in an individual with Robin sequence. In addition, mouse models have demonstrated haploinsufficiency of SATB2 results in craniofacial defects that phenocopy those caused by 2q32q33 deletion in humans; moreover, full functional loss of SATB2 amplifies these defects.^[7]

SATB2 expression is highly specific for cancer in the lower GI-tract and has been implicated as a cancer biomarker for colorectal cancer.^[9][10]

References

Further reading

• {{cite journal | vauthors = Dobreva G, Dambacher J, Grosschedl R | title = SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin mu gene expression | journal = Genes & Development | volume = 17 | issue = 24 | pages = 3048–61 | date = December 2003 | pmid = 14701874 | pmc = 305257 | doi = 10.1101/gad.1153003 }}
• {{cite journal | vauthors = Dobreva G, Chahrour M, Dautzenberg M, Chirivella L, Kanzler B, Fariñas I, Karsenty G, Grosschedl R | title = SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation | journal = Cell | volume = 125 | issue = 5 | pages = 971–86 | date = June 2006 | pmid = 16751105 | doi = 10.1016/j.cell.2006.05.012 }}
• {{cite journal | vauthors = Alcamo EA, Chirivella L, Dautzenberg M, Dobreva G, Fariñas I, Grosschedl R, McConnell SK | title = Satb2 regulates callosal projection neuron identity in the developing cerebral cortex | journal = Neuron | volume = 57 | issue = 3 | pages = 364–77 | date = February 2008 | pmid = 18255030 | doi = 10.1016/j.neuron.2007.12.012 }}
• {{cite journal | vauthors = Beaty TH, Hetmanski JB, Fallin MD, Park JW, Sull JW, McIntosh I, Liang KY, Vanderkolk CA, Redett RJ, Boyadjiev SA, Jabs EW, Chong SS, Cheah FS, Wu-Chou YH, Chen PK, Chiu YF, Yeow V, Ng IS, Cheng J, Huang S, Ye X, Wang H, Ingersoll R, Scott AF | title = Analysis of candidate genes on chromosome 2 in oral cleft case-parent trios from three populations | journal = Human Genetics | volume = 120 | issue = 4 | pages = 501–18 | date = November 2006 | pmid = 16953426 | doi = 10.1007/s00439-006-0235-9 }}
• {{cite journal | vauthors = Machado RD, Pauciulo MW, Fretwell N, Veal C, Thomson JR, Vilariño Güell C, Aldred M, Brannon CA, Trembath RC, Nichols WC | title = A physical and transcript map based upon refinement of the critical interval for PPH1, a gene for familial primary pulmonary hypertension. The International PPH Consortium | journal = Genomics | volume = 68 | issue = 2 | pages = 220–8 | date = September 2000 | pmid = 10964520 | doi = 10.1006/geno.2000.6291 }}
• {{cite journal | vauthors = Jugessur A, Shi M, Gjessing HK, Lie RT, Wilcox AJ, Weinberg CR, Christensen K, Boyles AL, Daack-Hirsch S, Nguyen TT, Christiansen L, Lidral AC, Murray JC | title = Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia | journal = PLoS One | volume = 5 | issue = 7 | pages = e11493 | year = 2010 | pmid = 20634891 | pmc = 2901336 | doi = 10.1371/journal.pone.0011493 }} {{open access}}
• {{cite journal | vauthors = Carter TC, Molloy AM, Pangilinan F, Troendle JF, Kirke PN, Conley MR, Orr DJ, Earley M, McKiernan E, Lynn EC, Doyle A, Scott JM, Brody LC, Mills JL | title = Testing reported associations of genetic risk factors for oral clefts in a large Irish study population | journal = Birth Defects Research. Part A, Clinical and Molecular Teratology | volume = 88 | issue = 2 | pages = 84–93 | date = February 2010 | pmid = 19937600 | pmc = 3503531 | doi = 10.1002/bdra.20639 }}
• {{cite journal | vauthors = Rosenfeld JA, Ballif BC, Lucas A, Spence EJ, Powell C, Aylsworth AS, Torchia BA, Shaffer LG | title = Small deletions of SATB2 cause some of the clinical features of the 2q33.1 microdeletion syndrome | journal = PLoS One | volume = 4 | issue = 8 | pages = e6568 | year = 2009 | pmid = 19668335 | pmc = 2719055 | doi = 10.1371/journal.pone.0006568 }} {{open access}}
• {{cite journal | vauthors = Vieira AR, Avila JR, Daack-Hirsch S, Dragan E, Félix TM, Rahimov F, Harrington J, Schultz RR, Watanabe Y, Johnson M, Fang J, O'Brien SE, Orioli IM, Castilla EE, Fitzpatrick DR, Jiang R, Marazita ML, Murray JC | title = Medical sequencing of candidate genes for nonsyndromic cleft lip and palate | journal = PLoS Genetics | volume = 1 | issue = 6 | pages = e64 | date = December 2005 | pmid = 16327884 | pmc = 1298935 | doi = 10.1371/journal.pgen.0010064 }} {{open access}}

External links

• {{UCSC genome browser|SATB2}}
• {{UCSC gene details|SATB2}}

Registry of SATB2 cases http://satb2gene.com

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