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Centre for Arab Genomic Studies a Division of Sheikh Hamdan Award for Medical Sciences Centre for Arab Genomic Studies A Division of Sheikh Hamdan Award for Medical Sciences The Catalogue for Transmission Genetics in Arabs CTGA Database Lysine-Specific Methyltransferase 2A Alternative Names transcriptional activation. KMT2A hence positively KMT2A regulates the transcription of several target genes Myeloid/Lymphoid or Mixed Lineage Leukemia such as HOXA9. It is also involved in the control of Gene circadian gene expression, PPP1R15A-induced MLL apoptosis, cell proliferation and haematopoiesis. MLL1 Trithorax, Drosophila, Homolog of The MLL gene is also a frequent target for TRX1 translocations. These rearrangements can lead to HRX the fusion of the MLL gene with over 50 different Myeloid/Lymphoid Leukemia Gene partners. The resultant fusion proteins are able to Mixed Lineage Leukemia Gene transform hematopoietic cells into leukemia stem ALL1 Gene cells and hence MLL rearrangements have been ALL1 implicated in Acute Myeloid Leukemia (AML), CXXC Finger Protein 7 Acute Lymphoblastic Leukemia (ALL) and Mixed CXXC7 Lineage (biphenotypic) Leukemia (MLL). Record Category Further, mutations in the gene have been associated Gene locus with Wiedemann-Steiner Syndrome (WDSTS), a multi-system disorder characterized by WHO-ICD hypertrichosis cubiti, short stature, intellectual N/A to gene loci disability and distinct facial dysmorphia. KMT2A mutations have also recently been implicated in Incidence per 100,000 Live Births Kabuki Syndrome 2 (KABUK2), an intellectual N/A to gene loci disability condition known for its distinct facies of long palpebral fissures and eversion of the lateral OMIM Number third of the lower eyelid. 159555 Molecular Genetics Mode of Inheritance The KMT2A gene is located on the long arm of N/A to gene loci chromosome 11. It spans a length of 90.3 kb of DNA and its coding sequence is contained within Gene Map Locus 37 exons. The protein product encoded by this gene 11q23.3 has a molecular mass of 431.7 kDa and consists of 3969 amino acids. Multiple isoforms of the Description KMT2A gene exist due to alternatively spliced The KMT2A gene encodes Lysine-Specific transcript variants. The gene is widely expressed in Methyltransferase 2A, a large nuclear protein the human body, with overexpression seen in the belonging to the myeloid/lymphoid or mixed- peripheral blood mononuclear cells, adipocyte, B- lineage leukemia (MLL) family. The protein lymphocyte and CD8 T-cells. Heterozygous de functions as an enzyme and is responsible for novo mutations in the gene, including deletions and catalyzing the methylation of the Lysine-4 residue nonsense mutations, have been linked to of histone H3, a process required for epigenetic Wiedemann-Steiner Syndrome. 1 Copyright © Centre for Arab Genomic Studies Alqassmi A, Almugbel M, AlQuaiz M, Alsaman A, Epidemiology in the Arab World Al-Thihli K, Sulaiman RA, Al-Dekhail W, Alsaegh Saudi Arabia A, Bashiri FA, Qari A, Alhomadi S, Alkuraya H, Monies et al. (2017) reported the findings of 1000 Alsebayel M, Hamad MH, Szonyi L, Abaalkhail F, diagnostic panels and exomes carried out at a next Al-Mayouf SM, Almojalli H, Alqadi KS, Elsiesy H, generation sequencing lab in Saudi Arabia. One Shuaib TM, Seidahmed MZ, Abosoudah I, Akleh patient, a 4-year-old female, suffered from skeletal H, AlGhonaium A, Alkharfy TM, Al Mutairi F, dysplasia, ribs fusion, ear deformity, cleft palate, Eyaid W, Alshanbary A, Sheikh FR, Alsohaibani absent uterus and vagina and choanal atresia. The FI, Alsonbul A, Al Tala S, Balkhy S, Bassiouni R, phenotype resembled a CHARGE-like presentation, Alenizi AS, Hussein MH, Hassan S, Khalil M, however, a multigene panel for Tabarki B, Alshahwan S, Oshi A, Sabr Y, dysmorphology/skeletal dysplasia identified a de- Alsaadoun S, Salih MA, Mohamed S, Sultana H, novo heterozygous mutation (c.3248G>A, Tamim A, El-Haj M, Alshahrani S, Bubshait DK, p.R1083Q) in exon 4 of the patient’s KMT2A gene, Alfadhel M, Faquih T, El-Kalioby M, Subhani S, associated with Kabuki syndrome. This case Shah Z, Moghrabi N, Meyer BF, Alkuraya FS. The highlighted the benefit of molecular testing in the landscape of genetic diseases in Saudi Arabia based diagnosis of overlapping clinical syndromes. on the first 1000 diagnostic panels and exomes. Hum Genet. 2017 Aug;136(8):921-939. PMID: References 28600779. Monies D, Abouelhoda M, AlSayed M, Alhassnan Z, Alotaibi M, Kayyali H, Al-Owain M, Shah A, Related CTGA Records Rahbeeni Z, Al-Muhaizea MA, Alzaidan HI, Kabuki Syndrome 2 (OMIM 300867) Cupler E, Bohlega S, Faqeih E, Faden M, Alyounes B, Jaroudi D, Goljan E, Elbardisy H, Akilan A, External Links Albar R, Aldhalaan H, Gulab S, Chedrawi A, Al http://www.genecards.org/cgi- Saud BK, Kurdi W, Makhseed N, Alqasim T, El bin/carddisp.pl?gene=KMT2A Khashab HY, Al-Mousa H, Alhashem A, Kanaan I, Algoufi T, Alsaleem K, Basha TA, Al-Murshedi F, Contributors Khan S, Al-Kindy A, Alnemer M, Al-Hajjar S, Sayeeda Hana Alyamani S, Aldhekri H, Al-Mehaidib A, Arnaout 28.09.2017 R, Dabbagh O, Shagrani M, Broering D, Tulbah M, 2 Copyright © Centre for Arab Genomic Studies .
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