t(6;20)(q13;q12) LMBRD1/CHD6
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| Written | 2014-04 | Nathalie Douet-Guilbert, Etienne De Braekeleer, Corinne Tous, Nadia Guéganic, Frédéric Morel, Marc De Braekeleer |
| Cytogenetics Laboratory, Faculty of Medicine, University of Brest, France |
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1. Identity
| ICD-Topo | C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS |
| ICD-Morpho | 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS |
| ICD-Morpho | 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable |
| ICD-Morpho | 9989/3 Myelodysplastic syndrome, unclassifiable |
| Atlas_Id | 1678 |
2. Clinics and Pathology
| Disease | Myelodysplastic syndrome/myeloproliferative disorder (MDS/MPD) in transformation (Acute myelocytic leukemia - AML) |
| Epidemiology | No cases registered in the Mitelman database. |
| Clinics | A 78-year-old woman seen because of worsening of cytopenias two years following diagnosis of MDS/MPD. No further investigations. |
| Evolution | Patient deceased soon after diagnosis of AML. |
3. Cytogenetics
| Note | The t(6;20)(q13;q12) involves two genes, the LMBRD1 and CHD6 genes, that have never been shown to form a fusion gene. |
| Cytogenetics Morphological | t(6;20)(q13;q12) is identified by banding cytogenetics. |
 | |
| RHG banding showing chromosomes 6 and 20 and the derivatives der(6) and der(20). | |
| Cytogenetics Molecular | To determine the position of the breakpoints on chromosomes 6 and 20, BACs located in the bands of interest were used as probes in FISH experiments. Analysis with RP11-359N1 showed that one signal hybridized to the normal chromosome 6, and the other split and hybridized to both der(6) and der(20). Analysis with RP11-257H6 showed that one signal hybridized to the normal chromosome 20, and the other split and hybridized to both der(6) and der(20). Co-hybridization with both BAC clones showed two fusion signals. RP11-359N1 contains the LMBRD1 gene and RP11-257H6 the CHD6 gene. |
 | |
| FISH with BACs RP11-359N1 (spectrum green, located in 6q13 and containing LMBRD1) and RP11-257H6 (spectrum orange, located in 20q12 and containing CHD6) showing co-hybridization. | |
4. Genes involved and Proteins
| Gene Name | LMBRD1 (LMBR1 domain containing 1) |
| Location | 6q13 |
| Note | Mutations in the LMBRD1 gene is responsible for methylmalonic aciduria and homocystinuria type cblF (autosomal recessive disorder). It is a disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin and methylcobalamin due to accumulation of free cobalamin in lysosomes, thus preventing its conversion to cofactors. Clinical features include poor feeding, failure to thrive, developmental delay, stomatitis, glossitis, seizures, macrocytic anemia, neutropenia, thrombocytopenia and methylmalonic aciduria responsive to vitamin B12. |
| Dna / Rna | The LMBRD1 gene contains 15 exons, spanning 115 kb. Three transcripts (splice variants) are known, two being protein coding. |
| Protein | The protein has 540 amino acids (61.4 kDa) and localizes to the lysosome membrane. It contains nine transmembrane helices and six putative glycosylation sites with an N terminus in the lysosomal interior and a cytoplasmatic C terminus. It is a probable lysosomal cobalamin transporter, being required to export cobalamin from lysosomes, which in turn allows its conversion to cofactors. It also appears to play a key role in mediating and regulating the endocytosis of the insulin receptor. Isoform 3 coding the nuclear export signal interacting protein (NESI) may play a role in the assembly of hepatitis delta virus. |
| Gene Name | CHD6 (chromodomain helicase DNA binding protein 6) |
| Location | 20q12 |
| Note | The CHD6 gene, located 403 kb centromeric to STS marker D20S108 is constantly deleted in MDS and MPD associated with del(20q) or ider(20q). |
| Dna / Rna | The CHD6 gene contains 37 exons of which 36 are coding, spanning 216 kb. Nine transcripts are known. |
| Protein | The gene encodes a member of the SNF2/RAD54 helicase protein family. The protein has 2715 amino acids (305 kDa) and localizes to the nucleus. It contains two chromodomains, a helicase domain, and an ATPase domain. The protein is thought to be a core member of one or more of chromatin remodelling complexes. It may function as a transcriptional repressor. It is involved in the cellular repression of influenza virus replication and in transcriptional repression of papillomavirus. |
5. To be noted
| Additional cases are needed to delineate the epidemiology of this rare entity: you are welcome to submit a paper to our new Case Report section. |
6. Bibliography
| CHD6 chromatin remodeler is a negative modulator of influenza virus replication that relocates to inactive chromatin upon infection. |
| Alfonso R, Lutz T, Rodriguez A, Chavez JP, Rodriguez P, Gutierrez S, Nieto A. |
| Cell Microbiol. 2011 Dec;13(12):1894-906. doi: 10.1111/j.1462-5822.2011.01679.x. Epub 2011 Sep 30. |
| PMID 21899694 |
| Fluorescence in situ hybridization characterization of ider(20q) in myelodysplastic syndrome. |
| Douet-Guilbert N, Lai JL, Basinko A, Gueganic N, Andrieux J, Pollet B, Plantier I, Delattre C, Crepin O, Corm S, Le Bris MJ, Morel F, De Braekeleer M. |
| Br J Haematol. 2008 Dec;143(5):716-20. doi: 10.1111/j.1365-2141.2008.07436.x. Epub 2008 Oct 21. |
| PMID 19036015 |
| Interaction of the papillomavirus E8--E2C protein with the cellular CHD6 protein contributes to transcriptional repression. |
| Fertey J, Ammermann I, Winkler M, Stoger R, Iftner T, Stubenrauch F. |
| J Virol. 2010 Sep;84(18):9505-15. doi: 10.1128/JVI.00678-10. Epub 2010 Jul 14. |
| PMID 20631145 |
| Insights into lysosomal cobalamin trafficking: lessons learned from cblF disease. |
| Gailus S, Hohne W, Gasnier B, Nurnberg P, Fowler B, Rutsch F. |
| J Mol Med (Berl). 2010 May;88(5):459-66. doi: 10.1007/s00109-010-0601-x. Epub 2010 Feb 20. (REVIEW) |
| PMID 20174775 |
| A novel mutation in LMBRD1 causes the cblF defect of vitamin B(12) metabolism in a Turkish patient. |
| Gailus S, Suormala T, Malerczyk-Aktas AG, Toliat MR, Wittkampf T, Stucki M, Nurnberg P, Fowler B, Hennermann JB, Rutsch F. |
| J Inherit Metab Dis. 2010 Feb;33(1):17-24. doi: 10.1007/s10545-009-9032-7. Epub 2010 Feb 3. |
| PMID 20127417 |
| Nuclear export signal-interacting protein forms complexes with lamin A/C-Nups to mediate the CRM1-independent nuclear export of large hepatitis delta antigen. |
| Huang C, Jiang JY, Chang SC, Tsay YG, Chen MR, Chang MF. |
| J Virol. 2013 Feb;87(3):1596-604. doi: 10.1128/JVI.02357-12. Epub 2012 Nov 21. |
| PMID 23175358 |
| CHD6 is a DNA-dependent ATPase and localizes at nuclear sites of mRNA synthesis. |
| Lutz T, Stoger R, Nieto A. |
| FEBS Lett. 2006 Oct 30;580(25):5851-7. Epub 2006 Oct 2. |
| PMID 17027977 |
| The Chd family of chromatin remodelers. |
| Marfella CG, Imbalzano AN. |
| Mutat Res. 2007 May 1;618(1-2):30-40. Epub 2007 Jan 21. (REVIEW) |
| PMID 17350655 |
| Novel splice site mutations and a large deletion in three patients with the cblF inborn error of vitamin B12 metabolism. |
| Miousse IR, Watkins D, Rosenblatt DS. |
| Mol Genet Metab. 2011 Apr;102(4):505-7. doi: 10.1016/j.ymgme.2011.01.002. Epub 2011 Jan 14. |
| PMID 21303734 |
| LMBRD1: the gene for the cblF defect of vitamin B12 metabolism. |
| Rutsch F, Gailus S, Suormala T, Fowler B. |
| J Inherit Metab Dis. 2011 Feb;34(1):121-6. doi: 10.1007/s10545-010-9083-9. Epub 2010 May 6. (REVIEW) |
| PMID 20446115 |
| CHD5 defines a new subfamily of chromodomain-SWI2/SNF2-like helicases. |
| Schuster EF, Stoger R. |
| Mamm Genome. 2002 Feb;13(2):117-9. |
| PMID 11889561 |
| LMBD1 protein serves as a specific adaptor for insulin receptor internalization. |
| Tseng LT, Lin CL, Tzen KY, Chang SC, Chang MF. |
| J Biol Chem. 2013 Nov 8;288(45):32424-32. doi: 10.1074/jbc.M113.479527. Epub 2013 Sep 27. |
| PMID 24078630 |
| Novel nuclear export signal-interacting protein, NESI, critical for the assembly of hepatitis delta virus. |
| Wang YH, Chang SC, Huang C, Li YP, Lee CH, Chang MF. |
| J Virol. 2005 Jul;79(13):8113-20. |
| PMID 15956556 |
7. Citation
| This paper should be referenced as such : |
| N Douet-Guilbert, Braekeleer E De, C Tous, N Guénic, F Morel, Braekeleer M De |
| t(6;20)(q13;q12) LMBRD1/CHD6 |
| Atlas Genet Cytogenet Oncol Haematol. 2014;18(12):954-956. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://atlasgeneticsoncology.usal.es/classic/Anomalies/t0620q13q12ID1678.html |
8. Translocations implicated (Data extracted from papers in the Atlas)
9. External links
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| All articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Nov 28 16:18:41 CET 2018 |
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