Iyini i - Chromosomal Deletion Syndrome?
Context:Izinkinga zokususwa kwama- chromosome ziwumphumela wokususwa kwezingxenye zama- chromosome. Kuye ngendawo, ubukhulu, nokuthi ukususwa kwezakhi zofuzo kudluliselwa kubani, kunezinhlobo ezimbalwa ezaziwayo zokususwa kwezakhi zofuzo. Ngokuvamile, ama-chromosomal deletion syndromes ahlanganisa ukususwa kwezakhi zofuzo ezinkulu ezibonakala lapho kusetshenziswa izindlela zokubhala i-karyotyping. Ukususwa okuncane kuholela ku-Microdeletion syndrome, okutholakala ngokusebenzisa i-fluorescence in situ hybridization (FISH)  Izibonelo ze-chromosomal deletion syndromes zihlanganisa i-5p-Deletion (cri du chat syndrome), i-4p-Deletion (i-Wolf<unk>Hirschhorn syndrome), i-Prader<unk>Willi syndrome, kanye ne-Angelman syndrome.
Izinkinga zokususwa kwama- chromosome ziwumphumela wokususwa kwezingxenye zama- chromosome. Kuye ngendawo, ubukhulu, nokuthi ukususwa kwezakhi zofuzo kudluliselwa kubani, kunezinhlobo ezimbalwa ezaziwayo zokususwa kwezakhi zofuzo. Ngokuvamile, ama-chromosomal deletion syndromes ahlanganisa ukususwa kwezakhi zofuzo ezinkulu ezibonakala lapho kusetshenziswa izindlela zokubhala i-karyotyping. Ukususwa okuncane kuholela ku-Microdeletion syndrome, okutholakala ngokusebenzisa i-fluorescence in situ hybridization (FISH)  Izibonelo ze-chromosomal deletion syndromes zihlanganisa i-5p-Deletion (cri du chat syndrome), i-4p-Deletion (i-Wolf<unk>Hirschhorn syndrome), i-Prader<unk>Willi syndrome, kanye ne-Angelman syndrome.  Isisekelo se - chromosomal se - Cri du chat syndrome siqukethe ukususwa kwengxenye yokugcina yengalo emfushane ye - chromosome 5. Ukususwa kwe-5p, kungakhathaliseki ukuthi kungokugcina noma okuphakathi, kwenzeka ezindaweni ezahlukene zokuphumula; isisekelo se-chromosomal ngokuvamile siqukethe ukususwa engxenyeni emfushane ye-chromosome 5. Ukuhlukahluka okubonwa phakathi kwabantu kungabangelwa umehluko wezinhlobo zabo zofuzo. Njengoba kwenzeka cishe ku-1 kwabangu-15.000 kuya ku-1 kwabangu-50.000 abazalwa bephila, kusikisela ukuthi kungenye yezinkinga ezivame kakhulu zokuqothulwa kwezakhi zofuzo ezihambisanayo. Ukususwa kwe-5p kuvame kakhulu ukuvela kwe-de novo, okuvela kubaba ezimweni ezingama-80 kuya ku-90%, okungenzeka ukuthi kubangelwa ukuphuka kwe-chromosome ngesikhathi sokwakheka kwe-gamete kwabesilisa.  Ezinye izibonelo zezici ezingase zibe khona ze-dysmorphic zihlanganisa: ukuvuleka kwe-palpebral, ibhuloho lomphimbo elibanzi, i-microcephaly, izindlebe eziphansi, amathegi e-preauricular, ubuso obuyindilinga, intamo emfushane, i-micrognatia, kanye ne-dental malocclusionhypertelorism, ama-epicanthal folds, amakhona aphansi omlomo. Ayikho inhlanganisela ekhethekile etholakele phakathi kobukhulu bokususwa nobunzima bezici zomtholampilo ngoba imiphumela ihluka kakhulu.  Isisekelo se - chromosomal se - Wolf - Hirschhorn syndrome (WHS) siqukethe ukususwa kwengxenye yokugcina yengalo emfushane ye - chromosome 4. Ingxenye esusiwe yezilwane ezibikiwe imelela cishe ingxenye yengalo ye-p, eyenzeka kude nama-band 4p15.1-p15.2. Umngcele oseduze we-WHSCR wachazwa ngokususwa kokuphela kwe-1.9 megabase ka-4p16.3. Le allele ihlanganisa izakhi zofuzo ezihlongozwayo i-LEMT1 ne-WHSC1. Lokhu kwabonwa ngabantu ababili ababonisa zonke izingxenye ezine ze-WHS phenotype eyisisekelo, okwenza ososayensi bakwazi ukulandelela i-loci yezakhi zofuzo ezisusiwe. Imibiko eminingi iphawuleka ngokukhethekile ngokubukeka kwesakhiwo se-craniofacial (isihlathi esivelele, i-hypertelorism, ibhuloho lomphimbo elibanzi eliqhubekela esiphongweni) okuye kwaholela egameni elichazayo elithi 'ukubukeka kwesigqoko sokuzivikela seqhawe lamaGreki.'"  Kunobufakazi obuningi bokuthi i-phenotype eyinhloko ye-WHS (ukubambezeleka kokukhula, ukukhubazeka kwengqondo, ukuquleka, nezici ezihlukile ze-craniofacial) kungenxa yokungasebenzi kahle kwezakhi zofuzo eziningana ezihlobene kakhulu ngokungafani ne-gene eyodwa. Amagciwane ahlobene nomthelela ekuguqukeni ahlanganisa:  I-WHSC1 ihlanganisa isifunda se-genomic esingu-90kb, izingxenye ezimbili kwezintathu zazo zise-telomeric ekupheleni kwe-WHCR; I-WHSC1 ingadlala indima ebalulekile ekuthuthukiseni okujwayelekile. Cishe ukususwa kwayo kunomthelela ku-WHS phenotype. Kodwa-ke, ukuhluka kobukhulu kanye ne-phenotype ye-WHS kusikisela izindima ezingaba khona zofuzo eziseduzane futhi ezikude ne-WHSCR. I-WHSC2 (eyaziwa nangokuthi i-NELF-A) ihilelekile ezicini eziningi zokucubungula i-mRNA kanye nomjikelezo weseli I-SLBP, i-gene e-encode i-Stem Loop Binding Protein, ihlala i-telomeric ku-WHSC2, futhi idlala indima ebalulekile ekulawuleni ukuhlanganiswa kwe-histone nokutholakala ngesikhathi sesigaba S. I-LETM1 ekuqaleni yayiphakanyiswe njengegene elungele ukuhlaselwa yisifo sokuwa; isebenza ngokushintshanisa ama-ion ngezindima ezingaba khona ekuthumeleni izimpawu zamaseli nasekukhiqizeni amandla. I-FGFRL1, efaka i-fibroblast growth factor decoy receptor, iye yabandakanyeka ku-craniofacial phenotype futhi mhlawumbe nezinye izici zamathambo, nokuma okufushane kwe-WHS. Muva nje i-CPLX1 iye yasikiselwa njengegene elingasetshenziswa ekutholeni isifo sokuwa e-WHS.  I- Prader-Willi (PWS) ne- Angelman syndrome (AS) yizinkinga ezihlukile ze- neurogenetic ezibangelwa ukususwa kwe- chromosomal, i- uniparental disomy noma ukulahleka kokuvezwa kwe- imprinted gene esifundeni se-15q11-q13. Ukuthi umuntu ubonisa i-PWS noma i-AS kuncike ekutheni kukhona yini ukuntuleka kofuzo oluvezwe ubaba ukufaka isandla esifundeni. [ isidingo ]  Ngokuvamile i-PWS itholakala iyimbangela yokukhuluphala okwesibili ngenxa ye-hyperphagia yokuqala - ukwanda okungavamile kwesifiso sokudla. Kunezimbangela ezintathu ezaziwayo zamangqamuzana zokuthuthukiswa kwePrader-Willi syndrome. Enye yazo iqukethe ukususwa okuncane kwesifunda se-chromosome 15q11<unk>q13. I-70% yeziguli inokususwa okungu-5<unk>7-Mb de novo esifundeni esiseduze kwe-chromosome kababa 15. Ukungajwayelekile kwesibili okuvamile kwezakhi zofuzo (~ 25-30% wamacala) yi-maternal uniparental disomy ye-chromosome 15. Le nqubo ibangelwa ukungahlukaniswa kwe-mitotic non-disjunction elandelwa ukulahleka kwe-mitotic kwe-chromosome kababa 15 ngemuva kokuvundiswa. Imbangela yesithathu ye-PWS ukuphazamiseka kwenqubo yokwakheka kwe-chromosome 15 eyindlalifa evela kubaba (izici ze - epigenetic). Lokhu kuphazamiseka kutholakala cishe kubantu abangu- 2 - 5% abathintekayo. Ngaphansi kuka-20% wabantu abanokukhubazeka kokuphrinta kutholakala ukuthi banokususwa okuncane kakhulu esifundeni sesikhungo sokuphrinta se-PWS, esisekupheleni kwe-5 'kwegene le-SNRPN.  I-AS iyisifo sokukhula kwezinzwa esibi kakhulu esibonakaliswa ukuphazamiseka kwengqondo, ukukhubazeka ekukhulumeni, ukuquleka, ukungasebenzi kahle kwezimoto, kanye nokwanda okukhulu kwe-autism. Umsuka kababa wezakhi zofuzo ezithintekayo kulesi sifo ubalulekile ngoba isifunda esithile se-chromosome 15 esihilelekile sinomthelela ekufakweni kwe-parent-of-origin, okusho ukuthi ngenxa yezakhi zofuzo eziningana kule ndawo, ikhophi eyodwa kuphela yezakhi zofuzo iyavezwa kuyilapho enye ithuliswa ngokufaka uphawu. Ezakhiweni zofuzo ezithintekile kuyi-PWS, ngokuvamile yikhophi kamama eyenza i-imprint (futhi ngaleyo ndlela ithulisiwe), kuyilapho ikhophi kayise eguqulwe izakhi zofuzo ingasebenzi.