Mikrodelecijski sindrom

Mikrodelecijski sindromi jesu sindromi koji su posljedica hromosomskim delecija manjih od pet miliona baznih parova (5 Mb), koji obuhvataju po nekoliko gena. Premalene su da bi se mogale otkriti uobičajenim citogenetičkim metodima ili analizom kariotipa visoke rezolucije (2–5 Mb).^[1]^[2] Detekcija se obavlja se pomoću fluorescentne in situ hibridizacije (FISH). Veći sindrom hromozomske delecije mogu se otkriti pomoću tehnika analize kariotipa.

Pregled

Mikrodelecijski sindromi su rezultat gubitka malog segmenta hromosoma specifične hromosomske lokalizacije. U literaturi se ponekada označavaju i terminom segmentalna aneusomija (čime se naglašava strukturna i funkcionalna monosomija zahvaćenog hromosomskog segmenta) kao i terminom sindrom susjednih gena (engl. contiguous gene syndrome). Kao i sve delecije, i mikrodelecije mogu biti intersticijske (interkalarne) ili terminalne.

Mikrodelecijski sindromi su heterogena skupina entiteta sa specifičnim kliničkim manifestacijama. Za neke od mikrodelecijskih sindroma je poznat uzrok koji može biti posljedica mutacije ili gubitka jednog gena uz autosomno dominantan tip nasljeđivanja (npr. Alagille sindrom), ili, pak, mutacije više susjednih gena (npr. Williams, Langer-Giedion i Miller-Dieker sindromi).

Danas je poznat veliki broj mikrodelecijskih sindroma sa različitom, a često i nepoznatom, frekvencijom pojavljivanja. Među najfrekventnije mikrodelecijske sindrome spadaju Miller-Dieker, Smith-Magenis, sindrom delecije 22q11.2, Prader-Willi, Angelman i Williams sindrom.

Za postavljanje dijagnoze mikrodelecijskih sindroma, pored kliničkih ispitivanja, koriste se različite metode analize genoma koje uključuju klasične citogenetičke metode diferencijalnog bojenja hromosoma, fluorescentnu in situ hibridizaciju - FISH, ali i molekularno-genetičke metode. Ove metode se međusobno dopunjuju i omogućavaju precizniji uvid u poremećaje genoma osoba s mikrodelecijskim sindromima.^[3]

Primjeri

DiGeorgeov sindrom ili velokardiofacijalni sindrom ^[4] – najčešći mikrodelecijski sindrom
Prader–Willijev sindrom^[5]^[6]
Angelmanov sindrom^[5]
Neurofibromatoza tip I^[7]
Neurofibromatoza tip II^[8]^[9]
Williamsov sindrom^[10]
Miller–Diekerov sindrom^[11]
Smith–Magenisov sindrom^[12]
Rubinstein–Taybijev sindrom^[13]
Wolf–Hirschhornov sindrom^[14]

Također pogledajte

Reference

^ H. William Taeusch; Roberta A. Ballard; Christine A. Gleason; Mary Ellen Avery (2005). Avery's Diseases of the Newborn. Elsevier Health Sciences. str. 210–215. ISBN 0-7216-9347-4.
^ "Microdeletion syndrome". Genetics Home Reference. 17. 4. 2014. Pristupljeno 19. 4. 2014.
^ Ibrulj S., Haverić S., Haverić A. (2008): Citogenetičke metode – Primjena u medicini. Institut za genetičko inženjerstvo i biotehnologiju (INGEB), Sarajevo, ISBN 978-9958-9344-5-2.
^ Shaikh, TH; Kurahashi, H; Saitta, SC; O'Hare, AM; Hu, P; Roe, BA; Driscoll, DA; McDonald-McGinn, DM; Zackai, EH; Budarf, ML; Emanuel, BS (1. 3. 2000). "Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis". Human Molecular Genetics. 9 (4): 489–501. doi:10.1093/hmg/9.4.489. PMID 10699172.
^ ^a ^b Buiting, K; Saitoh, S; Gross, S; Dittrich, B; Schwartz, S; Nicholls, RD; Horsthemke, B (april 1995). "Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15". Nature Genetics. 9 (4): 395–400. doi:10.1038/ng0495-395. PMID 7795645.
^ Runte, M; Varon, R; Horn, D; Horsthemke, B; Buiting, K (februar 2005). "Exclusion of the C/D box snoRNA gene cluster HBII-52 from a major role in Prader-Willi syndrome". Human Genetics. 116 (3): 228–30. doi:10.1007/s00439-004-1219-2. PMID 15565282.
^ Pasmant, E; Sabbagh, A; Spurlock, G; Laurendeau, I; Grillo, E; Hamel, MJ; Martin, L; Barbarot, S; Leheup, B; Rodriguez, D; Lacombe, D; Dollfus, H; Pasquier, L; Isidor, B; Ferkal, S; Soulier, J; Sanson, M; Dieux-Coeslier, A; Bièche, I; Parfait, B; Vidaud, M; Wolkenstein, P; Upadhyaya, M; Vidaud, D; members of the NF France, Network (juni 2010). "NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype". Human Mutation. 31 (6): E1506-18. doi:10.1002/humu.21271. PMID 20513137. Arhivirano s originala, 20. 9. 2021. Pristupljeno 19. 6. 2021.
^ Rouleau, GA; Merel, P; Lutchman, M; Sanson, M; Zucman, J; Marineau, C; Hoang-Xuan, K; Demczuk, S; Desmaze, C; Plougastel, B (10. 6. 1993). "Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2". Nature. 363 (6429): 515–21. Bibcode:1993Natur.363..515R. doi:10.1038/363515a0. PMID 8379998.
^ Beck, Megan; Peterson, Jess F.; McConnell, Juliann; McGuire, Marianne; Asato, Miya; Losee, Joseph E.; Surti, Urvashi; Madan-Khetarpal, Suneeta; Rajkovic, Aleksandar; Yatsenko, Svetlana A. (maj 2015). "Craniofacial abnormalities and developmental delay in two families with overlapping 22q12.1 microdeletions involving the gene". American Journal of Medical Genetics Part A. 167 (5): 1047–1053. doi:10.1002/ajmg.a.36839. PMID 25810350.
^ Tassabehji, M; Metcalfe, K; Karmiloff-Smith, A; Carette, MJ; Grant, J; Dennis, N; Reardon, W; Splitt, M; Read, AP; Donnai, D (januar 1999). "Williams syndrome: use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes". American Journal of Human Genetics. 64 (1): 118–25. doi:10.1086/302214. PMC 1377709. PMID 9915950.
^ Huang, HC; Bautista, SL; Chen, BS; Chang, KP; Chen, YJ; Wuu, SW (1996). "Miller-Dieker syndrome with microdeletion of chromosome 17p13.3: report of one case". Zhonghua Minguo Xiao Er Ke Yi Xue Hui Za Zhi [Journal]. Zhonghua Minguo Xiao Er Ke Yi Xue Hui. 38 (6): 472–6. PMID 9473821.
^ Bi, W; Yan, J; Stankiewicz, P; Park, SS; Walz, K; Boerkoel, CF; Potocki, L; Shaffer, LG; Devriendt, K; Nowaczyk, MJ; Inoue, K; Lupski, JR (maj 2002). "Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse". Genome Research. 12 (5): 713–28. doi:10.1101/gr.73702. PMC 186594. PMID 11997338.
^ Wójcik, C; Volz, K; Ranola, M; Kitch, K; Karim, T; O'Neil, J; Smith, J; Torres-Martinez, W (februar 2010). "Rubinstein-Taybi syndrome associated with Chiari type I malformation caused by a large 16p13.3 microdeletion: a contiguous gene syndrome?". American Journal of Medical Genetics Part A. 152A (2): 479–83. doi:10.1002/ajmg.a.33303. PMID 20101707.
^ Rauch, A; Schellmoser, S; Kraus, C; Dörr, HG; Trautmann, U; Altherr, MR; Pfeiffer, RA; Reis, A (1. 4. 2001). "First known microdeletion within the Wolf-Hirschhorn syndrome critical region refines genotype-phenotype correlation". American Journal of Medical Genetics. 99 (4): 338–42. doi:10.1002/ajmg.1203. PMID 11252005.

Dopunska literatura

H. William Taeusch; Roberta A. Ballard; Christine A. Gleason; Mary Ellen Avery (2005). Avery's Diseases of the Newborn. Elsevier Health Sciences. str. 210–215. ISBN 0-7216-9347-4.
Microdeletions and Molecular Genetics
Microdeletion syndromes (chromosomes 1 to 11) on UpToDate
List of 100 microdeletion/duplication syndromes detected by array-CGH Arhivirano 29. 6. 2021. na Wayback Machine on GENOMA
Schwartz, Stuart; Graf, Michael D. (Sep 13, 2002). "Ch 19. Microdeletion Syndromes: Characteristics and Diagnosis". Molecular Cytogenetics : Protocols and Applications. Methods in Molecular Biology. 204. str. 275–290. doi:10.1385/1-59259-300-3:275. PMID 12397804.
Vissers, LE; Stankiewicz, P (2012). "Microdeletion and microduplication syndromes". Methods in Molecular Biology. 838: 29–75. doi:10.1007/978-1-61779-507-7_2. ISBN 978-1-61779-506-0. PMID 22228006.

Vanjski linkovi

* Slavotinek, Anne (2012). "Microdeletion Syndromes". eLS. doi:[//doi.org/10.1002%2F9780470015902.a0005549.pub2 10.1002/9780470015902.a0005549.pub2. ISBN 978-0470016176.uve-never-heard-of/ 13 chromosomal disorders you may not have heard of]
http://atlasgeneticsoncology.org/Educ/MicrodeletionID30059ES.html (en)
http://www.uptodate.com/contents/microdeletion-syndromes-chromosomes-1-to-11 (en)
http://www.friendshipcircle.org/blog/2012/05/22/13-chromosomal-disorders-youve-never-heard-of/ (en)

[TaeuschBallard2005-1] H. William Taeusch; Roberta A. Ballard; Christine A. Gleason; Mary Ellen Avery (2005). Avery's Diseases of the Newborn. Elsevier Health Sciences. str. 210–215. ISBN 0-7216-9347-4.

[2] "Microdeletion syndrome". Genetics Home Reference. 17. 4. 2014. Pristupljeno 19. 4. 2014.

[Ibrulj_S_(2008)-3] Ibrulj S., Haverić S., Haverić A. (2008): Citogenetičke metode – Primjena u medicini. Institut za genetičko inženjerstvo i biotehnologiju (INGEB), Sarajevo, ISBN 978-9958-9344-5-2.

[4] Shaikh, TH; Kurahashi, H; Saitta, SC; O'Hare, AM; Hu, P; Roe, BA; Driscoll, DA; McDonald-McGinn, DM; Zackai, EH; Budarf, ML; Emanuel, BS (1. 3. 2000). "Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis". Human Molecular Genetics. 9 (4): 489–501. doi:10.1093/hmg/9.4.489. PMID 10699172.

[pmid7795645-5] Buiting, K; Saitoh, S; Gross, S; Dittrich, B; Schwartz, S; Nicholls, RD; Horsthemke, B (april 1995). "Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15". Nature Genetics. 9 (4): 395–400. doi:10.1038/ng0495-395. PMID 7795645.

[6] Runte, M; Varon, R; Horn, D; Horsthemke, B; Buiting, K (februar 2005). "Exclusion of the C/D box snoRNA gene cluster HBII-52 from a major role in Prader-Willi syndrome". Human Genetics. 116 (3): 228–30. doi:10.1007/s00439-004-1219-2. PMID 15565282.

[7] Pasmant, E; Sabbagh, A; Spurlock, G; Laurendeau, I; Grillo, E; Hamel, MJ; Martin, L; Barbarot, S; Leheup, B; Rodriguez, D; Lacombe, D; Dollfus, H; Pasquier, L; Isidor, B; Ferkal, S; Soulier, J; Sanson, M; Dieux-Coeslier, A; Bièche, I; Parfait, B; Vidaud, M; Wolkenstein, P; Upadhyaya, M; Vidaud, D; members of the NF France, Network (juni 2010). "NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype". Human Mutation. 31 (6): E1506-18. doi:10.1002/humu.21271. PMID 20513137. Arhivirano s originala, 20. 9. 2021. Pristupljeno 19. 6. 2021.

[8] Rouleau, GA; Merel, P; Lutchman, M; Sanson, M; Zucman, J; Marineau, C; Hoang-Xuan, K; Demczuk, S; Desmaze, C; Plougastel, B (10. 6. 1993). "Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2". Nature. 363 (6429): 515–21. Bibcode:1993Natur.363..515R. doi:10.1038/363515a0. PMID 8379998.

[9] Beck, Megan; Peterson, Jess F.; McConnell, Juliann; McGuire, Marianne; Asato, Miya; Losee, Joseph E.; Surti, Urvashi; Madan-Khetarpal, Suneeta; Rajkovic, Aleksandar; Yatsenko, Svetlana A. (maj 2015). "Craniofacial abnormalities and developmental delay in two families with overlapping 22q12.1 microdeletions involving the gene". American Journal of Medical Genetics Part A. 167 (5): 1047–1053. doi:10.1002/ajmg.a.36839. PMID 25810350.

[10] Tassabehji, M; Metcalfe, K; Karmiloff-Smith, A; Carette, MJ; Grant, J; Dennis, N; Reardon, W; Splitt, M; Read, AP; Donnai, D (januar 1999). "Williams syndrome: use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes". American Journal of Human Genetics. 64 (1): 118–25. doi:10.1086/302214. PMC 1377709. PMID 9915950.

[11] Huang, HC; Bautista, SL; Chen, BS; Chang, KP; Chen, YJ; Wuu, SW (1996). "Miller-Dieker syndrome with microdeletion of chromosome 17p13.3: report of one case". Zhonghua Minguo Xiao Er Ke Yi Xue Hui Za Zhi [Journal]. Zhonghua Minguo Xiao Er Ke Yi Xue Hui. 38 (6): 472–6. PMID 9473821.

[12] Bi, W; Yan, J; Stankiewicz, P; Park, SS; Walz, K; Boerkoel, CF; Potocki, L; Shaffer, LG; Devriendt, K; Nowaczyk, MJ; Inoue, K; Lupski, JR (maj 2002). "Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse". Genome Research. 12 (5): 713–28. doi:10.1101/gr.73702. PMC 186594. PMID 11997338.

[13] Wójcik, C; Volz, K; Ranola, M; Kitch, K; Karim, T; O'Neil, J; Smith, J; Torres-Martinez, W (februar 2010). "Rubinstein-Taybi syndrome associated with Chiari type I malformation caused by a large 16p13.3 microdeletion: a contiguous gene syndrome?". American Journal of Medical Genetics Part A. 152A (2): 479–83. doi:10.1002/ajmg.a.33303. PMID 20101707.

[14] Rauch, A; Schellmoser, S; Kraus, C; Dörr, HG; Trautmann, U; Altherr, MR; Pfeiffer, RA; Reis, A (1. 4. 2001). "First known microdeletion within the Wolf-Hirschhorn syndrome critical region refines genotype-phenotype correlation". American Journal of Medical Genetics. 99 (4): 338–42. doi:10.1002/ajmg.1203. PMID 11252005.

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