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    Topic review

    SALL4 Gene

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    Submitted by: Karina Chen
    (This entry belongs to Entry Collection "MedlinePlus ")

    Definition

    spalt like transcription factor 4

    1. Normal Function

    The SALL4 gene is part of a group of genes called the SALL family. These genes provide instructions for making proteins that are involved in the formation of tissues and organs during embryonic development. SALL proteins are transcription factors, which means they attach (bind) to specific regions of DNA and help control the activity of particular genes.

    The exact function of the SALL4 protein remains unclear. Based on the functions of similar proteins in other organisms (such as zebrafish and mice), the SALL4 protein appears to play a critical role in the developing limbs. This protein may also be important for the development of nerves that control eye movement and for the formation of the walls (septa) that divide the heart into separate chambers.

    2. Health Conditions Related to Genetic Changes

    2.1. Duane-radial ray syndrome

    More than 25 mutations in the SALL4 gene have been identified in people with Duane-radial ray syndrome (also known as Okihiro syndrome) or a very similar condition called acro-renal-ocular syndrome. Researchers suspect that Duane-radial ray syndrome and acro-renal-ocular syndrome are part of an overlapping set of syndromes with many possible signs and symptoms.

    Most SALL4 gene mutations create a premature stop signal in the instructions for making the SALL4 protein. As a result, cells do not produce any functional protein from one copy of this gene. Researchers are investigating how a reduction in the amount of the SALL4 protein disrupts eye, heart, and limb development in people with Duane-radial ray syndrome and acro-renal-ocular syndrome.

    2.2. Other disorders

    A least one mutation in the SALL4 gene has been found to cause IVIC syndrome, a condition whose signs and symptoms overlap with those of Duane-radial ray syndrome and acro-renal-ocular syndrome. The acronym IVIC stands for Instituto Venezolano de Investigaciones Cientìficas, the center where the condition was first described. Major features of IVIC syndrome include abnormally formed bones in the arms and hands, hearing loss, and problems with eye movement caused by abnormalities of the muscles that surround the eyes (extraocular muscles).

    The SALL4 gene mutation responsible for IVIC syndrome creates a premature stop signal in the instructions for making the SALL4 protein. As a result, cells produce an abnormally short version of the protein from one copy of this gene. It is unclear whether this shortened protein is completely nonfunctional or if it retains some of its function as a transcription factor. Researchers are working to determine how this SALL4 gene mutation disrupts early development and leads to the characteristic features of IVIC syndrome.

    3. Other Names for This Gene

    • dJ1112F19.1
    • DRRS
    • HSAL4
    • MGC133050
    • sal (Drosophila)-like 4
    • sal-like 4
    • sal-like 4 (Drosophila)
    • SALL4_HUMAN
    • spalt-like transcription factor 4
    • Zinc finger protein SALL4
    • ZNF797

    The entry is from https://medlineplus.gov/genetics/gene/sall4

    References

    1. Al-Baradie R, Yamada K, St Hilaire C, Chan WM, Andrews C, McIntosh N, NakanoM, Martonyi EJ, Raymond WR, Okumura S, Okihiro MM, Engle EC. Duane radial raysyndrome (Okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family. Am J Hum Genet. 2002 Nov;71(5):1195-9.
    2. Borozdin W, Boehm D, Leipoldt M, Wilhelm C, Reardon W, Clayton-Smith J, BeckerK, Mühlendyck H, Winter R, Giray O, Silan F, Kohlhase J. SALL4 deletions are acommon cause of Okihiro and acro-renal-ocular syndromes and confirmhaploinsufficiency as the pathogenic mechanism. J Med Genet. 2004 Sep;41(9):e113.
    3. Harvey SA, Logan MP. sall4 acts downstream of tbx5 and is required forpectoral fin outgrowth. Development. 2006 Mar;133(6):1165-73.
    4. Kohlhase J, Chitayat D, Kotzot D, Ceylaner S, Froster UG, Fuchs S, Montgomery T, Rösler B. SALL4 mutations in Okihiro syndrome (Duane-radial ray syndrome),acro-renal-ocular syndrome, and related disorders. Hum Mutat. 2005Sep;26(3):176-83.
    5. Kohlhase J, Heinrich M, Schubert L, Liebers M, Kispert A, Laccone F, TurnpennyP, Winter RM, Reardon W. Okihiro syndrome is caused by SALL4 mutations. Hum MolGenet. 2002 Nov 1;11(23):2979-87.
    6. Kohlhase J. SALL4-Related Disorders. 2004 Aug 16 [updated 2015 Jan 15]. In:Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A,editors. GeneReviews® [Internet]. Seattle (WA): University of Washington,Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1373/
    7. Koshiba-Takeuchi K, Takeuchi JK, Arruda EP, Kathiriya IS, Mo R, Hui CC,Srivastava D, Bruneau BG. Cooperative and antagonistic interactions between Sall4and Tbx5 pattern the mouse limb and heart. Nat Genet. 2006 Feb;38(2):175-83.
    8. Miertus J, Borozdin W, Frecer V, Tonini G, Bertok S, Amoroso A, Miertus S,Kohlhase J. A SALL4 zinc finger missense mutation predicted to result inincreased DNA binding affinity is associated with cranial midline defects andmild features of Okihiro syndrome. Hum Genet. 2006 Mar;119(1-2):154-61.
    9. Paradisi I, Arias S. IVIC syndrome is caused by a c.2607delA mutation in theSALL4 locus. Am J Med Genet A. 2007 Feb 15;143(4):326-32.
    10. Terhal P, Rösler B, Kohlhase J. A family with features overlapping Okihirosyndrome, hemifacial microsomia and isolated Duane anomaly caused by a novelSALL4 mutation. Am J Med Genet A. 2006 Feb 1;140(3):222-6.
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