ęඈඋ1࣏ۘऺ ৰ 19 Ż ৰ 24 ƛ 20150611 ϦČ Chinese Journal of Tissue Engineering Research June 11, 2015 Vol.19, No.24 www.CRTER.org
Pierre RobinÛǍּ͟ȖüՈۘऺ^ẟʉ
˸┌͔ ̜ůʥ(˂hãîȰij˂hưȈ½¶¬Ŝ́ãKŲà˂hď 210008)
তͥ ǍʻPierre Robin ÛǍ(Pierre Robin Sequence PRS)«PඈÑɃ@мƮ3აȒżǎZ ƻ_:K˿K1990 ˝ÛKک<Ǹ⒲LՈ 1 ʀȼ̓⓿&ĽǍՈ̴ͅɳмƮ ͢҉üǎǕ҉ƶ:ɎƦܲ dz࿁^̶Ȗüƅ͟4 ŲàœďNK˩ȂK ˂hãîÝŸœþK Ȍ4SOX9 Ȗü3KCNJ2 তʺ¤Ո,ǍʻতՈĽͥńzȭ Pierre Robin ÛǍּ͟ȅọȖüẟᜐ 2 ƶϙÎāưȈ¶¬Ŝ́K ȖüÑǎ LAR ǪK‼›Ȗü Ptprs ʐ Ptprf dz࿁&☢වȌǍɳ Pierre Robin ÛǍՈȅọȖü4 Pierre Robin ͥƩŘ̡Ͳ /~ÖàϬՈ͛5তֲՈ& Pierre Robin ÛǍȅọȖüՈۘऺȴƇֲʃȖüzĹͥ ܲ Pierre Robin Ά9Ά9˵ʩΡ 3 ÛǍՈ҉üǎǕ҉ƶ: & Pierre Robin ÛǍՈQ)ʐਟɡȴƇ,ɩᲳ4 ͟⏲᪑ ȁ·ȔŀYÓɷʆKœþK ƶQåKΡ~ÛĕåK ඈඋȀņඈඋ1࣏Ƀ@мƮPierre Robin ÛǍॅǜȖüĹͥ ˂hãîȰij˂hư 'L᪑ Ȉ½¶¬Ŝ́ãKŲ Ƀ@мƮॅǜȖüἛČĹͥ à˂hď 210008
ʼᡅ Ě ିǻ:R318 A:ۅDzʃ ྐëPierre Robin ÛǍ(Pierre Robin Sequence PRS)«PඈÑɃ@мƮ3აȒżǎZʀȼ̓⓿&Ľ তේǻ:2095-4344 ǍՈ̴ͅɳмƮ ĠǕေឆ4ֲQęͱ̲ȭ Pierre Robin ÛǍǕ҉ƶ:ՈۘऺɎƦܲǎĽǎՈȅọȖü4 (2015)24-03910-06 SOX9 Ȗü3KCNJ2 ȖüÑǎ LAR ǪK‼›Ȗü Ptprs ʐ Ptprf dz࿁^☢වȌǍɳ PRS ּ͟4 ɘ4ěY2015-04-15 Ոȭęͱ̲ȭ Pierre Robin ÛǍּ͟ȖüՈۘऺɆPවẴ & Pierre Robin ÛǍȅọȖüՈۘऺȴ http://WWW.crter.orgֲ
ƇֲʃȖüzĹͥ4 5ͩàϬᩥਜ਼ƶ̼௦ęƛ͔ϔǒß(CNKI)ʐ PubMed ϔǒß 1999 À 1 ƄႷ 2014 À 9 Ƅּ͟
Dz 58 ઋ4ńʃLʐʼᡅÑ8Ƀ@мƮ Pierre Robin ÛǍ ॅǜ ȖüĹͥ9z8micrognathia Pierre Robin Sequence mutation gene locus9&̼௦᪑ẟᜐ̼௦ ₑͥȭ 58 ઋতẟᜐ Ȍ4
Ș^SOX9 Ȗü3KCNJ2 ȖüÑǎ LAR ǪK‼›Ȗü Ptprs ʐ Ptprf dz࿁&☢වȌǍɳ Pierre Robin ▊ÛǍՈȅọȖü4ẕÀǡ ęͱ̲ȭ]Ġƅ͢ÂிඣмƮՈ Pierre Robin ÛǍּ͟ȖüՈۘऺ'ᡅ
ȌÑǎּ͟¬ĭµ z 17q2324 ẝPľǻ ̶&Ƀʳƨ҉ŷۘऺ Ɏ◄ẟᜐẟPǹՈ̓ʳƨǒɀʐ҉ŷ ƧẟPǹ ȌẝȖüń Pierre Robin ÛǍՈǕ҉ƶ:ՈňϬ º໐ܲ Pierre Robin ÛǍՈ҉üǎ
Ǖ҉ƶ:4
.ůʥ. Pierre Robin ÛǍּ͟ȖüՈۘऺ^ẟʉ[J].ęඈඋ1࣏ۘऺ 2015 19(24):3910-3915̜ ͔┌˸ doi:10.3969/j.issn.2095-4344.2015.24.026
Pierre Robin sequence related genes
Tang Chen-lu, Shen Wei-min (Department of Burn and Plastic Surgery, Nanjing Children’s Hospital Affiliated to Nanjing Medical University, Nanjing 210008, Jiangsu Province, China)
Tang Chen-lu, Studying for Abstract master’s degree, Department of BACKGROUND: Pierre Robin Sequence is a congenital malformation which is characterized by micrognathia, Burn and Plastic Surgery, glossoptosis and respiratory tract obstruction with or without cleft palate. SOX9, KCNJ2, Ptprs and Ptprf are Nanjing Children’s Hospital probably connected with Pierre Robin Sequence. Affiliated to Nanjing Medical OBJECTIVE: To review the recent progress in the researches on the related genes about Pierre Robin University, Nanjing 210008, Sequence. Jiangsu Province, China METHODS: A computer-based online search of CNKI database and PubMed database was performed to retrieve the relevant articles published from January 1999 to September 2014 with the key words of “micrognathia, Pierre Corresponding author: Shen Wei-min, Master, Chief Robin Sequence, mutation, gene locus” in Chinese and English, respectively. Finally, 58 articles were included physician, Master’s supervisor, for review after deleting unrelated and repetitive ones. Department of Burn and Plastic RESULTS AND CONCLUSION: SOX9, KCNJ2, Ptprs and Ptprf are probably connected with Pierre Robin Surgery, Nanjing Children’s Sequence. Recently, the research on the genes connected with Pierre Robin Sequence focuses on 17q2324, Hospital Affiliated to Nanjing and small sample cases are commonly seen. But, further large sample test and case analysis, as well as related Medical University, Nanjing animal models are needed to analyze the role of these genes in the pathogenesis of Pierre Robin sequence, as 210008, Jiangsu Province, well as consequently, we can analyze the etiology and pathogenesis of Pierre Robin sequence. China
Accepted: 2015-04-15 Subject headings: Micrognathism; Mutation; Genes; Genetic Loci
3910 P.O. Box 10002, Shenyang 110180 www.CRTER.org
. Pierre Robin ÛǍּ͟ȖüՈۘऺ^ẟʉ www.CRTER.org ͔┌˸
Tang CL, Shen WM. Pierre Robin sequence related genes. Zhongguo Zuzhi Gongcheng Yanjiu. 2015;19(24): 3910-3915.
0 šᣄ Introduction ȅiſĝɰωĢ˄$̣ʳĢ˄ÖƀŌɴƎʷΛOω^ ̔ϔΈ́Ć˗ϔƃ̢̔ƒɡǓļĝΦɻbƷ¢ ƕKbǫ͉ưæ4uΓƘˊȌΈ́j̷ͻʭΈ́$Ɨŷ 3@KĆn˗ϔʘƷ¢^ƕƖƁKæĕƁ!İ\$ Έ́$̔ˇƷ¢^.$ƱbΈ́ġ[4K11-13]0Pierre Robin ƷÚ3@ÖƀDΟŌɴ̣ʳàǼ0Pierre RobinͥƩŘ ͥƩŘĝƍƟ͛ȠȊ$Ŝ́Ȼã$Ʊ Λ̜ã$̵Û (Pierre Robin sequenceKPRS)ĆȆ̔ϔΈ́$Á ưãġƗãǸ˾ƍƟKƶϙɡLsΧęȁFΛȷ§ɰ ̢ǖΛ°̣ʳęɴȅɡǓŘĝ˝ǧ͇Έ́K@4ƷƑ ωǑƧK ϙð͛̓ĕĴƍƟKƯ4uƑƪĝPierre ƪ[1-3]0ȶD1923˝nƽˋ÷ψνPierre RobinƷ˫ RobinͥƩŘ͉ư͛ĉðY̓Ƒf́Ĵ0Ɨļ͉ưƀ| EɽĵKγɒcɡPierre RobinǸ˾ŘK̢uΡ~2ʌ ưΉð͛Y̓ΥΆƐKWuºļ͉ưlƍƟ̢WáÝ ΓĆn˗ϔʘƷ¢^ƕͿ3@̢ƒDƷĝˊƩ̢ͫ ̣ʳ$ɰω$ΥƷ¢İ\ΛÛAƷ¢v͇[4K14-17]0 ĝBʊ)3KʛȷcPierre-RobinͥƩŘ[4-5]0ƙĝƷÛ 2.2 ϋţƌǜPierre RobinįƌũǛ;ǰʢƘ Ċ ˼ ¦ǓļŰiNɜΡ~ƀRKĄWɫʌ:0ɻģ Pierre RobinͥƩŘΓƘǸ˾Řʕʩĝð̡KΓic ƋˋˍȻPierre RobinͥƩŘĝ˵ʩ̡ͲΆ9Ρ~ȓ ɡǜǸ˾Ř͇Pierre RobinͥƩŘ0êΉʩPierre ǸĵKɡPierre RobinͥƩŘ̡ͲΆ9ĝΡ~ǜɺʩ RobinͥƩŘĝ ¦Ρ~2ʌɲ16K1013K1618 ʲ/Ά9Ϳɲļĝ˵ʩ̸ʷ0 ˴AǠĝAǠ)3æˏΓ˵ʩKΓƏ2˴AǠ (2q24.133.3)K4˴AǠ(4q32qter)K11˴AǠ 1ᰈʐ5ͩData and methods (11q21q23.1)KΛ17˴AǠ(17q21q24.3)°ĝA 1.1 ºϗ̀ ijȔŀϗƔ1999˝1Åƀ2014˝9Å Ǡ)3ĆȋƗiQęĝKŃ̜AǠ)3ƶϙɡA ˵ʩɻˬKƏɻϗƔÅY̔ϔΈ́KPierre RobinͥƩ Ǡĝ$Ɨȧ$Ȕ)Λ ɲ[18-22]0 ŘKȔ)KΆ9ɲļZGɻϗƔÅmicrognathiaKPierre οƮġ[20]ȁˎƋ6ŸPRS͉ưY̓əŔƩ̱͛ϗ Robin SequenceKutationKgene locus0 !K;ĜƤ7ɩˠϦ$uξÝƲ),ĝCNVsKERɡ 1.2 ĤͩϤɉ lq43-q44$14q32.31 ƅæˏPRS2̀uʩ0]˝įK ൷͑ʃβƖĵˍ`Pierre RobinͥƩŘ˵ʩΆ9 ˋˍȻƋ^4uΓƘˊȌΈ́ĝPierre RobinͥƩŘ˵ ɱϝ˵ʩĝɻˬ0 ʩΆ9ĝΡ~ƶϙΚƏ17q2324Ń [18-19K23]0 Ƕ┨ʃβƗȧΡ~Λˍ`0_ĝɻˬ0 Jakobsenġ[24]ÝɲAǠ17q24.3ĝSOX9Ά9°s ᯬₓ᪈ĜϗĜĖɻˬ214͙KÇŸ/ǝ˼ċϙY 1.13 MbƷ˫ƅAſÝ5 kbˍĝͬ̑ ɲKERɡ ̓K̖Ρ~ʲĝÆɻʕʩĝ107͙Kʬļț̢ SOX9 Ά 9 ˼ Γ ˵ Ƴ ĝ KCNJ2 Ά 9 æ ˏ Pierre Λˍ`Ɨȧĝɻˬ49͙KLǍ58͙ɻˬȓY`ǫʭ0 RobinͥƩŘĝƷDuʩ0ϡuΡ~2ʌ"ˍFÖ°˵ ʩ(LAR)νȂěǠĉ"ō`žưžɍ(RPTPs)Ά9Ptprs 2ȘResults ˼Ptprf æͻͮDƷPierre-RobinͥƩϊǤɻΈ́[25]0 2.1 Pierre-Robinįƌũ^Łǜ Π Pierre Robinͥ 2.2.1 SOX9 Ά 9 ˼ KCNJ2 Ά 9 SOX9 Ά 9 ij ƩŘĝƷDȁÝ1/20 0001/8 500ŭϏ[5]KΓôn˗ϔ SRY(YAǠ͇5µş )˵ʩÔHMG(N·lÔ͇ ʘƷ¢^ƕͿ3@̢ƒDƷĝˊƩ̢ͫĝBʊ)30 ˮ ŵ ) ˿ Ά 9 ν Ȃ K ȋ ˝ Ć Ý N ś ȼ Ʒ ¢ 3 @ ȶΈ́æþŷáÝKϡæĆʦ̜ƗƷ$ȧÖ˝ǧ͇Έ (campomelic dysplasinKCD)ƏƷ˫0ȶΆ9ƶϙÚ ́ ĝ b ǫ K ȋ @ Ϧ ĝ Ć Stickler Ǹ ˾ Ř $ ͇5µş˼ǫ̼EÝ̰ƠƷ¢ˎiƏ ʘĝ́fE velocardiofacialǸ˾ŘΛTreacher-CollinsǸ˾Ř[5-7]0 ÚÒlˊȌΛˮĝƷ¢0ÆȻKȶΆ9ϡƖǏġ ĊPierre RobinͥƩŘΓƘǸ˾Řʕʩĝð̡KΓi ΝDĝƷÛuʩ0SOX9Ά9%ȢͥƩĝȔ)æĕƁN cɡǜǸ˾Ř͇Pierre RobinͥƩŘ0 śpʘƷ¢^ƕ$͇5ǫ̼İ\˵ʩĝʘǠƷ¢3@ Pierre RobinͥƩŘĝD9˼ƷD·ƅʲν±ɫí ġ[26-27]0NśĝSOX9Ά9şɲAǠ17q24.325.1 ǫ KƗRɡϔʘĝ·̨͇Ίͷ$ ¦9ŵΛ̰Ơ ƅˍKAſ¿ɡ3 934 bpK˛uƖɩˍ˛ǰ0KCNJ2 ΉRǭƁΈɒɚ9ŵuʩKϡuQęcˇȼɷˏİ\ Ά9şɲij17˴AǠ17q23K%Ȣˍ̇Ŝǐσȁę æˏĆPierre RobinͥƩŘĝƷD·ƅ[8]0ΓĽ̀Ʋ Kir2.1 Θþɲ[24 K 28]0ʲνĝΡ~2ʌKCNJ2Ά9Ć 2˫ɡ̔˗ϔ$Á̢ǖΛƑƪKΓƏ˗ϔʘƷ¢^ƕ AndersenǸ˾ŘƁDΆ90SOX9Ά9˼KCNJ2Ά9ɡ ϖbȋɡʌ˩Kg˫Ǔġĝɻ`0ƑƪĝƷÛȁ¿ 17˴AǠ°˵ƳĝƖɩΆ9KƖŀŭϏuA¿ĝ ɡ90%KƗɡ^Ƀ.͇Ƒƪ0͆ubǫ͉ư4uΑz 1.9 MbĝΆ9ʡKɲȶ ĝȔ)æˏPierre Ʒ¢^.[9-10]0ƗļPierre RobinͥƩŘ͉ưų4u^ RobinͥƩŘ˵ʩ[21K29]0
ISSN 2095-4344 CN 21-1581/R CODEN: ZLKHAH 3911
. Pierre Robin ÛǍּ͟ȖüՈۘऺ^ẟʉ www.CRTER.org ͔┌˸
Toshikiġ[30]QęƤŸPierre RobinͥƩŘ˾EȤ ŀƏƷ˫SOX9Ά95`ƂĝΆ9Ɨ̖KɡSOX9Ά9¹i ǞˍǂȀĝDŸKEƷ˫ΓSOX9Ά9áÝæĕƁpʘ ŐõȔ)ǜɺƤɩ̵ĝɲļ[38]0 Ʒ¢İ\ĝȔ)KEÚΓ˗sĝCOL2A1ĝ2ê0 SOX9ÝêΉˇÒlΤˍFƷ¢ˎiƏ2êĝ^Ȁ Amarilloġ[31]QęƤŸ͉uPierre RobinͥƩŘĝ18 æˏĕƁTreacher CollinsǸ˾Ř({c˗ϔɻƷ¢ Åƽ˿IKRɡSOX9Ά9ĝɲƂ̚KPRSƷD˵ʩ0 ^ƕKuǓŘ͇ĝɻϊɻ`)śţĝ4˲0TCOF1 Jakobsenġ[19K24]ÝɲAǠ17q24.3ĝSOX9Ά9° Ά9ĝȔ)Treacher CollinsǸ˾ŘuʩKȅðϡĕƁ s1.13MbƷ˫ƅAſÝ5kbˍĝͬ̑ ɲKERɡ GģPierre RobinͥƩŘÝˍĝΓƘǤɻΈ́0uŦʦ SOX9 Ά 9 ˼ Γ ˵ Ƴ ĝ KCNJ2 Ά 9 æ ˏ Pierre ôκ2ʌ2˫Pierre RobinͥƩŘ2̀ĝôκŦʦÝ RobinͥƩŘĝƷDuʩ0Benkoġ[32]ȁˎƋÝ3ɩ̲˵ Γ°Ƒ]˾ŭνΛ]˾ˎiƏKæÝƑ0ĝ°͓˗Ϗ ŷŻĝ^4uΓƘΈ́ĝPierre RobinͥƩŘνˊĝΡ Ɖˍϗ!ĖSox9 mRNAĝ2ê3@[39-40]KɯξţôƤ ~KƷ˫ɲSOX9Ά9ǢŜż1.23$1.18$1.07 Mb SOX9Ά9ÝŃȆŮ́Ƨ́fˎiƏuȔhĝæˏ ŭϏĝ3¡3ɲƆļ0Ń̜ļ2ʌƤÝSOX9˼ȋ]ĝ ͇0 Ŝ ż Ά 9 KCNJ2 ŭ Ϗ ĝ 1.9Mb ĝ Ά 9 ʡ Ə ̔ Pierre RobinͥƩŘƆļΚ=ǢŜż ȋ]ĝΆ 160 kbĝ ˍáÝɩPierre RobinͥƩŘuʩĝ 9ĆKCNJ2KŃΆ9%ȢɣsʘǠΌ˼̷ΌĝʗqŸ Ά9ƆƪļΚ˾0ƘɜȁˎƋ12ŸǜǸ˾Ř͇͉ŀĝϗ ŀɲĝˍ̇ŜǐσŦǰȁę[41]0KCNJ2%ȢͥƩĝȔ) !KƷ˫Ƥ3ɩΆ94æɲļYƖ¡ɲSOX9ĝǢŜ æĕƁ AndersenǸ˾ŘKŃǸ˾ŘĝǓļɡ̷Ȁæ żIˎ1.38 Mb¡Kdž¡ɲSOX9Ƃ1.52 Mb¡0 @$ƛΉ͇Ƭ͋ΛǓŘ͇Έ́KΓƏGģ̔ϔΈ́K ΓšæĝΆ9ǫ5A319 kb$75 kb$36 kb0 ̍æ2˫Ƒƪ[42]0ƯKcnj2Ά94æĝº˾ǰŊIJæ Selviġ[33]Ƌ27ŸPierre RobinͥƩŘ͉ŀY̓Ά 2˫5°Ƒƪ[43]0Ρ~2ʌKCNJ2˼SOX9Ά9mRNA 9(KƷ˫1ŸSOX9Ȼ˩ǰ14æ˼2ŸȻ˩ǰ24 ŋͬĝ2êĦPierre RobinͥƩŘuʩ[19]0 æ0ÆŭȻKƘɜ͆ϗ!Ƥ2ɩɲƆƪļΚ˾°s 2.2.2 LARνȂưžɍΆ9Ptprs˼Ptprf "ˍFÖ° ĝŷŻĝLėLJdzÝǠˍĝͻ͇0BˌţʌÝ ˵ʩ(LAR)νȂěǠĉ"ō`žưžɍ(RPTPs)æŐ ÛʦǠˍKǓ5ĆÝ2êSox9ĝ˗ϔʘˍFƏSox9Ά õō`žĝưž̼˼(ưž̼ͬ̑KÎƯÚ ȆŮ 9ɲļƛɞáÝAƉ)30B˾Ń̜Ρ~Bˌæȟ Ʒ¢˼ȆŮɿƧĝˍF̸˴0LAR RPTPsĆ˗ϔʘ˼ ƆSOX9Ά9ΛΓƛɞĝΆ9Ȇ ĝ͵͂ĆĕƁ °ϔʘŞ@Ʒ¢Ɩ ͛ĝ0Stewartġ[25]ƅaƤPtprsZ Pierre RobinͥƩŘĝɩ@Ϧ°90 PtprfΆ9͑č̔IJKƷ˫39%ĝPtprs−/−ZPtprf−/−̰ QęcƋǤÒlΤˍFƏSox9Ά9ĝY̓ǰ Ơ˫˗ϔΈ́0EϟŃ̜̰ƠÝ16.518.5Ơƽð¸ ̢KôκȆŊIJ2˫ƑƪΛnΤˍFǫ̼Ʒ¢ĝ 2˫̔ϔ˼°Ϙ4˲KGģƑƪ˼Ƒʘ3@0Ńƕ2 ǤɻpʘƷ¢^.[34]0ƯÝ.ÎȆŮͿˇÒlΤƏ ƅ ̀NśPierre-RobinͥƩŘ˵ţ0Ư˗ϔŞ@ĝ̰Ơ Sox9Ά92ê̢KôκŊIJõ2˫Ƒƪ˼˗ϔʘƷ¢ õɫ˫Ƒƪ˼Ϙʘ3@0LARνȂưžɍΆ94æ̔ ^ƕK2ʌÒlΤΛnÆƷ¢ƯfĝpʘĆnSox9 IJ2̀˼NśPierre-RobinǸ˾Říǫ˵ţK2ʌě Ά9Őõĝ[34-35]0ȅðKSox9ÝΑ̰ˇÒlΤƏĝˎſ LAR ư ž ɍ Ő õ ĝ ̸ ˴ ȁ Ǯ ˼ ˗ s ļ æ ˏ 2êzĕpʘÛfˎâ[36]KƯÝIJpʘˍFƏĝˎſ2 Pierre-RobinǸ˾ŘĝƷDˎi0Ptprs;PtprfňȔ)̔IJ êõĕƁôκŊIJ2˫Ƒƪ˼ƃɾ[37]0Ń̜Bˌ2ʌ æȁˎWnt˼ʘ́fĉ"̸˴ȁǮŐõ˗ϔf́˼ˍ Sox9ĝ2êŋͬŞ@˗ϔƷ¢Uɱƃˊ0B˾°ĵŦ FùŲ0ÝPierre-RobinǸ˾ŘƏæƷ˫ʘ́fĉ"2 ʦʖ̀Ρ~KΛÝ^4uΓƘΈ́ĝPierre Robinͥ ˼COL2A1ĝŐ;ǰSOX9¸ƷÛȔ)0LARνȂưž ƩŘĝ͉ŀƏ(ĝŐõSOX9Ά9ĝùό9ǰĝ3 ɍĆƕNśPierre-RobinǸ˾Ř̡ͲΆ9KƙƋPierre @2ʌNś˗ϔƷ¢^ƕ$ƑƪġPierre RobinͥƩŘ RobinǸ˾Ř͉ŀĝʘ́fĉ"˼Wnt̸˴ȁǮuʩϧ ĝǓŘ2̀æˏĆnÝƷ¢ˎiƏij}ɾpʘˍ Ȕh0 FϏƉƏSOX9þ_άƘ^ȀĕƁĝ09ÆKSOX9Ά9 2.3 ϋţƌǜũPierre RobinįƌũǛ;ǰʢƘ ÝǤɻpʘƷ¢́fˎiƏɪ"ΡĝȔ)¸æˏĕƁ Pierre RobinͥƩŘ@ȔɡΓƘǸ˾ŘĝƲ2˫ŭ Pierre RobinͥƩŘĝƷÛ0 Ư˫ÝΓƘǸ˾ŘƏKjStickler Ǹ˾ŘKƑ̷ɻǸ Ɓ>uΡ~2ʌSOX9Ά9Ɔļ°sĝùόǰæ ˾ŘKMarshall Ǹ˾ŘKTreacher Collins Ǹ˾ŘK ùξSOX9Ά9Ý˗ϔʘ́fˎiƏĝ2êKĄĆΓƘ Catel-Mancke Ǹ˾ŘKKabukiǸ˾ŘKNagerǸ˾ŘK bɲ˼8ƅSOX92êĝŐ;3@ΛȔ)ĕƁPierre teratogene Ǹ˾Řġ0ΓƏȋ@ϦĝĆSticklerǸ˾Ř$ RobinͥƩŘ2̀ĝæˏ±^ˏɃ.̖0]˝įuΡ velocardiofacialǸ˾ŘΛTreacherCollinsǸ˾Ř[5-6]0 ~Ý1Ÿ͉uPierre RobinͥƩŘΛȐϒƷ¢^.ĝ͉ Ń̜Ǹ˾Řĝ ¦Ǔļ˼þºĝPierre RobinͥƩŘ
3912 P.O. Box 10002, Shenyang 110180 www.CRTER.org
. Pierre Robin ÛǍּ͟ȖüՈۘऺ^ẟʉ www.CRTER.org ͔┌˸
ĆȆĆuʃȅĝf9͆ĆuDZΥĝǓļK͆uøY` )$ϟ4ɲļȔ)KŃ̜Ȕ)ΩTCOF1Ά9ĝ28ɩȻ Ρ~˼ƸƔ0 ˩ǰ̖Ʃ0ΓƏ4æȔ)$$nȔ)$ϟ4ɲļȔ)æ 2.3.1 SticklerǸ˾Ř SticklerǸ˾Řƕ@AǠ˩ DΟ ȢȔ)K9Ûν ĝƔŸɱȢǰKÎƯǜνƔŸ ͇ ¦°BķȆŮDK1965˝n˝Sticklerġ[44]Ė˝ Ƥĉ"ƉŤƍĝ˾f0Ρ~Ȍα˩ý]16%ĝTCSνȂ Qę0ȶǸ˾ŘĝƶϙǓŘ͇D)ɡάb$÷ɻb$ʩ áÝij24Ȼ˩ǰ5 bp4æȔ)KƯϟKÝ200ƕȔ)Ə ;D)ΛǸſƍ¬0Γ÷ɻbĝĽ̀ǓŘɡ̔ϔΈ́$ Iˎ50%ĝȔ)ΚƏÝȻ˩ǰ10K15K16K23K24K ɻƏb'ͬ$Ħ Ɠ$ƃ Λ ôν01/4ĝ͉ŀu 9ÆKŃ5ɩȻ˩ǰiȟ!ɡTCOF1Ά9ĝȔ)Kļ ƑŞƏƪ[45]0 0Conteġ[51]Ƌ46Ÿʕͻ¸ʩˊĝTCS͉ŀĝŜɩ SticklerǸ˾ŘĝƷD·ƅƶϙ°ĉ"%ȢΆ TCOF1%Ȣ Y̓!ͥ0Ʒ˫Ƥ15ɩ^ȅĝTCOF1Ȕ 9ĝȔ)uʩ0¿75%ĝSticklerǸ˾Ř͉ŀɡ4̀Fƀ )KGģ12ɩ̵ĝȔ)˼3ɩũĝȔ)0ȅðKƘɜ Ǡ2̀Kȶ̀ƶϙĆn5̀°ĉ"ĝ%ȢΆ9 ͆ϗ!ĖƤ7ƕ̵ĝ˼13ƕũĝΆ9ƗƧ͇0ƘɜÝ (COL2A1)ƷÛȔ)(ď Ȕ)$ϙΆƂ͈)ƖƁ[46]0COL ΓƏ1Ÿ͉ŀĝϊƏϗ!ĖɲȻ˩ǰ6ĝþϙΆǡ 2A1Ά9şɲ12q13.11-q13.2KA¿31 510 bpK˛54 õc.2859-30G > AKERɡŃɩ)3æˏfɡɩ̵ĝ ɩȻ˩ǰ0ΓƏij15Ȼ˩ǰ%Ȣ5̀ν°ĉ"ĝN TCOF1Ά9ĝϟ4Ȕ)0džȻKÝConteġĝΡ~Əu ƂKij648Ȼ˩ǰ%ȢȔͰBʊĝ˺̷ Kij4952 29Ÿ͉ŀƁuTCS2̀KĄƋΓTCOF1Ά9%Ȣ Ȼ˩ǰ%ȢCƂ0ƷÛCOL2A1Ά9Ȼ˩ǰ2ĝȔ)ȁ ĝ(EɫƷ˫ƁDȔ)0ΓȔ)æˏɲΆ9Őõ @ͮĕƁάb2˫Ưʕ.ΚǑKƯCOL2A1Ά9Ȼ˩ 0 ǰ2ȻĝȔ)@2˫ɡάbΛ.ÎĝD)0ŃĆn TCOF1Ά9ȻKDauwerseġ[52]Ʒ˫ƤƖɩ Ȼ˩ǰ2%Ȣĝαν°ƍƶϙáÝFƀǠƏKƯÝ Treacher CollinsǸ˾Ř˵ʩĝ ɃΆ9POLR1D ΓƘBķȆŮƏ˛ƘΖº[47]05̀FƀǠ2̀ĝStickler ˼POLR1C0ŃƖɩΆ9%ȢRNA˾ɍ4˼6ΘΆ[53]0 Ǹ˾Ř͉ŀ@ϦĝΆ9ȷ)ɲAǠlp21°ĝ%Ȣ ƘɜƋ242ŸTCS͉ŀΛΓȫʫY̓Ά9!ͥKÝΓƏ20 >̀°ĝΆ9(COL11A1)KȶΆ9%Ȣ>̀°ĝ Ÿ͉ŀĝϊƏϗ!Ė17ƕPOLR1DȔ)10ɩÖ˾ ǰƗŤƍa1(11)KƙĝȔ)DΟGģάÝˍĝ.Î͇Ʋ ĝʕ,Ȕ)˼7ɩÖ˾ĝè,Ȕ)0Ń̜è,Ȕ)ųɲ 2˫[45]0Ƥ°Ɩƕś̀ȻKCOL11A2Ά9ĝȔ Ȼ˩ǰ3KŃ G˛RNA˾ɍƵ̼ĝY̼Lė )ϡͮDΟSticklerǸ˾Ř0nΓ%Ȣĝĉ"ƍÝάb `Άž0Ń̜Ȕ)æˏȼH˺ǂǠ3ΘΆĝƵ̼0džȻK ^2êK9ÆȶΆ9Ȕ)ĕƁĝSticklerǸ˾ŘWu.Î ƘɜÝ3ŸνȂ͇TCS͉ŀĝϊƏϗ!ĖPOLR1CΆ9 šǑƯʕάb2˫[48]0 °ĕƁj`ž279ǡ͈ĝè,Ȕ)KŃ`ΆžĆ 2.3.2 Treacher-CollinsǸ˾Ř Treacher-CollinsǸ˾ POLR1CƵǠ̼BʊĝɩɒſLė`Άž0Ń̜Ρ Ř(TCS)K{cɻ˗ϔʘƷ¢^ƕǸ˾Ř(MSD)Ćƕ ~Bˌ2ʌPOLR1D ˼ POLR1CϡæˏĆTCSĝD9 ǤɻΈ́ɡƶϙǓŘĝ@AǠ˩͇ ¦D[49]0ƷD ŭ0ConteġĝΡ~Əĝ29ŸʕTCOF1Ά9Ȕ)ĝ͉ ȁ ¿ ɡ 1/50 000 K 60% ĝ D Ÿ ɡ Ʒ ˫ [50] 0 ŀKΓƁDΆ9ϡæˏɲŃ 0 Treacher-CollinsǸ˾ŘĝǓŘ͇Έ́2˫ɡɻʘΛ˗ 2.3.3 ΓƘ˵ʩǸ˾Ř Braddock-CareyǸ˾ŘĆ ϔƷ¢^ƕ$̔ƱΈ́$ɖƪȻ˗´$˗ɖ4ƍΛƱ ȆPierre RobinͥƩŘKŽŵǠƷ¢^.Kɻb˝ǧ νƷεɲ ġ[51]0 Έ́KƷ¢vƌΛ˝ǧ͇ͻ̔0ϠºšɡǓŘĝǸ˾ ʲνƋTreacher-Collins Ǹ˾ŘƷD·ƅĝΡ~Ɨ Ř0]įKBraddock-CareyǸ˾ŘiţʌĆn21q22 RɡTCOF1Ά9Ȕ)ĆTCSĝ ¦Ά0NTCOF1 AǠə4æDΟĝ0Ń GģRUNX1Ά9KΓ Ά9şɲAǠ5q31Mq34 Kʃn28ɩȻ˩ǰȆ þ_άƘ^ȀͮĕƁͻ̔0Ϡºĝ2˫[54]0Izumiġ[55] f0TCOF1%ȢTreacleĉ"KŃĉ" Ǡˍ˺ǂ QęƤʐƲ2˫ɡPierre-RobinͥƩŘKɻb3@K Ǡ9Û0Treacleĉ"æˏ°sB˾9ǰ(UBF)ʃ ˝ǧ̷͇ã4˲KĦſϠȤ˼ͻ̔0ϠºĝIưKEÝ ̼0UBFĆRNA˾ɍ4Ý˺MĝLJdz9ǰ0Ý̰ƠƷ Γ21q22ƅͫΆ94æǸ˾Ř ˍƷ˫1.9 Mbə4 ¢ΉϏTreacleĉ"Ýij1K2}ɾbɲɒ2ê0Treacle æ0Ƙɜş,ƤɩæˏáÝĕƁBraddock-CareyǸ˾ ĉ"4˲ĕƁæhĉ"Ɖǂ2ĝ˺ǂǠϠº0Ń˺ Ř̔ϔ2̀Ά9ĝȋ̔Ɨŗ KERɡɲȶ ĝ ǂǠ4ƻìĆ̰ƠƷ¢ˎiƏƋÒl°͓˼Òl ITSN1Ά9$SONΆ9$GARTΆ9æˏĆPRSĝ̡Ͳ Τȋîĝɚ˕K˳ƅƤŃ̜ɒſùŴĝˍFˍFƛΉY Ά90 iEzĕˍFŝɏ[52-53]0 AndersenǸ˾ŘĆȆ̷Ȁæ@$ƛΉ͇Ƭ͋ ΨRɡŸKƷ˫TCOF1Ά9ƁDȔ)u200Ɨ ΛǓŘ͇Έ́ɡǓļĝ@AǠ˩͇ ¦D0ΓǓŘ͇ ƕKΓƏîbǫɡ4æȔ)$$nȔ)$è,Ϳʕ,Ȕ Έ́GģʘƷ¢^ƕ$̔ϔΈ́$Ƒƪġ0ʲνƷ˫
ISSN 2095-4344 CN 21-1581/R CODEN: ZLKHAH 3913
. Pierre Robin ÛǍּ͟ȖüՈۘऺ^ẟʉ www.CRTER.org ͔┌˸
Iˎ20ɩKCNJ2Ȕ)æDΟAndersenǸ˾Ř[42]0 [5] Breugem CC, Mink van der Molen AB. What is Pierre Robin seque-nee. J Hast Reeonstr Aesthet Surg.2009; 62(12):1555- 2q34-qterΆ9ƗȧΛ4q34.2-qterΆ94ææDΟ 1558. ˊƩ˝ǧ͇Έ́KGģPierre Robin ͥƩŘ(PRS)$ [6] Ansari M, Rainger JK, Murray JE, et al. A syndromic form of ŪǠ3@$˝ǧ̷͇ãD(CHD)$Ʒ¢v͇˼Ɔˏİ\0 Pierre Robin sequence is caused by 5q23 deletions Aliġ[56]ȁˎƋʐƷ¢v͇͉ưĝƲ2̀˼Ά9ͥ encompassing FBN2 and PHAX. Eur J Med Genet.2014;57: 587-595. ƩY̓ǫʭKRɡ4q34.1q34.3ĝɩǓşĝ4 Mb [7] Costa MA, Tu MM, Murage KP, et al.Robin sequence: (174178 Mb)æˏĆPRSĝʩϧ 0 mortality, causes of death, and clinical outcomes. Plast ŖΛʘ́ƧƷÛĉ"2Ά9ĝ20p12.3ə4æDΟ Reconstr Surg.2014;134(4):738-745. ƑƪǸ˾Ř[57-58]0Sahooġ[57]QęƤƖɩ20p12.3ə4 [8] Abadie V, Morisseau-Durand MP, Beyler C, et al.Brainstem dysfunction: a possible neuroembryological pathogenesis of æɩǠ˼ɩƗõ20p12.3ə4æνǾ0Æ3ŸDŸu isolated Pierre Robin sequence.Eur J Pediatr.2002;161: ¿5.5 Mbĝ4æ(20p13p12.2)K3Ÿ͉ŀĝƲ2˫ɡ 275-280. ʌ˩ĝƑƪ˼ɻbΈ́KΓƏ2Ÿ͉ŀuPierre Robin [9] Antonarakis GS, Suri S. Prevalence and patterns of permanent tooth agenesis in patients with nonsyndromic ͥƩŘ2̀0 Pierre Robin sequence..Am J Orthod Dentofacial Orthop. 2014;145:452-460. 3ʉƗProspects [10] Evans AK, Rahbar R, Rogers GF, et al. Robin sequence: a ΨRɡŸƋPierre RobinͥƩŘ˵ʩΆ9ĝΡ~Ɨ retrospective review of 115 patients. Int J Pediatr Otorhinolaryngol. 2006;70(6):973-980. ɡ̔ϊĝôκΛDŸΡ~0SOX9Ά9$KCNJ2Ά [11] Stevenson DA, Carey JC. New Syndrome A Novel Multiple 9ΛLARνȂưžɍΆ9Ptprs˼PtprfæˏɡǜǸ˾ Congenital Anomaly–Mental Retardation Syndrome With Ř͇Pierre RobinͥƩŘĝ̡ͲΆ90COL2A1Ά9$ Pierre Robin Sequence and Cerebellar Hypoplasia in Two COL11AΆ9$OOL11A2Ά9(SticklerǸ˾Ř)KTCOF1 Sisters. Am J Med Genet A. 2007; 143A:2221-2226. [12] Thouvenin B, Djadi-Prat J, Chalouhi C,et al. Developmental Ά9$POLR1DΆ9$POLR1CΆ9(Treacher Collins outcome in Pierre Robin sequence: A longitudinal and Ǹ ˾ Ř ) K RUNX1 Ά 9 (BraddockCarey Ǹ ˾ Ř ) K prospective study of a consecutive series of severe KCNJ2Ά9(AndersenǸ˾Ř)æĕƁPRSɡ2̀ĝ phenotypes. Am J Med Genet. 2013;161A:312-319. [13] Daniel M, Bailey S, Walker K,et al. Airway, feeding and growth ɪƕȧÖĝ˝ǧ͇Έ́0ĄʲνƋΓ˵ʩΆ9ĝΡ~Ɨ in infants with Robin sequence and sleep apnoea. Int J ɡ̔ϊôκK±͛Y̓Y`ĝîϊôκ˼DŸǫ Pediatr Otorhinolaryngol.2013;77:499-503. ʭΛ˵ʩŦʦʖ̀Y`ǫʭŃ̜Ά9ÝPierre [14] Shen WM, Cui J, Chen JB, et al. Treatment of airway RobinͥƩŘĝƷD·ƅƏĝȔhKÎƯʌ:Pierre obstruction with mandibular distraction osteogenesis in Pierre Robin syndrome. Zhonghua Zheng Xing Wai Ke Za Zhi. 2010; RobinͥƩŘĝD9ΛƷD·ƅ0 1: 4-7 ύ,ɏξG. Pierre RobinවȌǍ¨̫ƛေឆƫȒʀȼ╠ݑՈڂ [15] ň້ᯥDzৰPň້ǀt᪂ᩥǎᰈΚ▊ ৰPň້t ̠า[J].ŒĿƚ๒ǭ๒ƚƾȣ,2012,18(2):146-147. [16] ጧäƸ,Ł͈,ᾕʎ.[@ɜ⍦ Ĺš͏ћ,ϣ̫RobinÛǍ Ởᩳň້Ǖʝ ৰPň້ȭতᯣᯧ4 Zʀȼ̓⓿Ո!ǹȆᩬ[J]. ÖɃ̫̲ƾȣ,2013,12(5): .֎Ξॅতǎͱǭ]5ǎּ͟-֎Ξॅ4 388-390,394- :Ēˊᡅ˖̵ƅ^ּ͟ĒˊȃΞॅՈͱǭ4 [17] Cladis F, Kumar A, Grunwaldt L, et al.Pierre Robin Sequence ƚƫƫ᪱Pierre Robin ÛǍ(Pierre Robin Sequence a perioperative review. Anesth Analg.2014;119(2):400-412. [18] Jamshidi N, Macciocca I, Dargaville PA, et al.Isolated Robin PRS)/«PඈÑɃ@мƮ3აȒżǎZʀȼ̓⓿&ĽǍՈ̴ sequence associated with a balanced t(2;17) chromosomal ͅɳмƮ ĠǕေឆ4 translocation. J Med Genet.2004;41:1. ň້̌ত&ƣ ň˅ \èे \͘Ǻǎึȑ [19] Jakobsen LP, Knudsen MA, Lespinasse J,et al.The genetic basis of the Pierre Robin Sequence.Cleft Palate Craniofac ǒ ᯧႮᯣ4ףʐc-uᩲ ͱǭǎϔǒ J.2006;43:155-159. [20] Ǥ˷,Ȗ⏪,ęʇ,.6ŷƅPierre RobinÛǍᜬƧՈ,ϣ̫ 4 džDz References ͔ȖüඈśᯡϔǜŎ Ȍ[J].ŒĐĿƚƾȣ,2011,14(11): 670-675. [1] Paladini D, Morra T, Teodoro A,et al. Objective diagnosis of [21] Tan TY, Farlie PG. Rare syndromes of the head and micrognathia in the fetus:the jaw index.Obstet Gynecol.1999; face-Pierre Robin sequence. WIREs Dev Biol.2013;2: 93:382-386. 369-377. [2] ǜᅷ.,ϣ̫Pierre RobinවȌǍ18ŷ Ö Ȍ[J].ɴÏ)^ [22] Tan TY, Kilpatrick N, Farlie PG. Developmental and genetic ͏ћ,2002,13(3):183-183. perspectives on Pierre Robin sequence. Am J Med Genet Ȍ Ïɶ,ᾱණȬ,£Ïࠒ,.Pierre Robin වȌǍ17ŷ Öٸ [3] Part C Semin Med Genet.2013;163C:295-305. [J].ęĿTƾȣ,2014,16(4):495-497. [23] Foster JW, Dominguez-Steglich MA, Guioli S,et al. ࣏ˮ,ȀņŒ.Pierre RobinÛǍՈۘऺẟʉ[J].ę┉̫ƚ Campomelic dysplasis and autosomal ses reversal caused by [4] 2010,37(6):565-567. mutations in an SRY-related gene.Nature.1994;372:525-530.
3914 P.O. Box 10002, Shenyang 110180 www.CRTER.org
. Pierre Robin ÛǍּ͟ȖüՈۘऺ^ẟʉ www.CRTER.org ͔┌˸
[24] Jakobsen LP, Ullmann R, Christensen SB,et al. Pierre Robin [42] Bendahhou S, Donaldson MR, Plaster NM, et alDefective sequence may be caused by dysregulation of SOX9 and po-tassium channel Kir2.1 trafficking underlies KCNJ2.J Med Genet.2007;44:381-386. Andersen-Tawil syndrome.J Biol Chem. 2003; 278(51): [25] Stewart K, Uetani N, Hendriks W, et al.Inactivation of LAR 51779-57785. family phosphatase genes Ptprs and Ptprf causes craniofacial [43] Zaritsky JJ, Eckman DM, Wellman GC, et al. Targeted malformations resembling Pierre-Robin sequence. disruption of Kir2.1 and Kir2.2 genes reveals the essential Development. 2013;140:3413-3422. role of the inwardly rectifying K(+) current in K(+)-mediated [26] ┌ම,ɏН,ɏގ.Sox9ȖüՈȀ3£࿁ǎẟĚ[J].ϣʁՈĚƚ, vasodilation.Circ Res.2000;87:160-166. 2012,32(4):310-315. [44] Stickler GB, Belau PG, Farrell FJ, et al.Hereditary progressive [27] Gordon CT, Attanasio C, Bhatia S, et al.Identification of novel arthro-ophthalmopathy. Mayo Clinic Proc.1965;40:433-455. craniofacial regulatory domains located far upstream of SOX9 [45] Snead MP, Yares JR. Clinical and molecular genetics of and disrupted in Pierre Robin sequence.Hum Mutat.2014; Stickier syndrome.J Med Genet.1999;36:353-359. 35(8):1011-1120. [46] Sncad MP, Payne SJ, Barton DE, et al.Stickler syndrome [28] De Baere E.Deciphering the cis-regulatory landscape of COlTelation between vitreoretinal phenotypes and linkage to SOX9 implicated in craniofacial development and isolated COL 2A1.Eye.1994;8:609-614. Pierre Robin sequence.Hum Mutat.2014;35(8):v [47] Reardon A, Sanddl L, Jones CJ, et al. Localization of pN-type [29] Sanchez-Castro M, Gordon CT, Petit F,et al. Congenital Heart II A procoUagen on adult bovine vitreous colhgen fibrils.Matrix Defects in Patients with Deletions Upstream of SOX9. Hum B.2000;19:169-173. Mutat. 2013;34(12):1628-1631 [48] Sirko-Osadsa DA, Murray MA, Scott JA, et al. Stickier [30] Takenouchi T, Matsuzaki Y, Yamamoto K, et al. SOX9 syndrome without eye involvement is causeed by mutations in dimerization domain mutation mimicking type 2 collagen C0L11A2.The geneencoding thealpha2.(K)chainoftypeK disorder phenotype. Eur J Med Genet. 2014;57(6):298-301. colagen. J Pediatr.1998;132:368-371. [31] Amarillo IE,Dipple KM, Quintero-Rivera F.Familial [49] Fazen LE, Elmore J, Nadler HL.Mandibulo. facial dysostosis microdeletion of 17q24.3. upstream of SOX9 is associated (Treacher CoHins syndrome).Am J Dis Child. 1967;113: with isolated Pierre Robin sequence due to position effect.Am 405-410. J Med Genet.2013;161A:1167-1172. [50] Jones KL ,Smith DW ,Harvey MA ,et al.Older paternal age [32] Benko S, Fantes JA, Amiel J,et al.Highly conserved and fresh gene mutation: data on additional disorders. J non-coding elements on either side of SOX9 associated with Pediatr.1975;86:84-88. Pierre Robin sequence.Nat Genet.2009;41:359-364. [51] Conte C, D'Apice MR, Rinaldi F, et alNovel mutations of [33] Selvi R, Mukunda Priyanka A. Role of Sox9 in the etiology of TCOF1 gene in European patients with treacher Collins Pierre-Robin Syndrome. Iran J Basic Med Sci.2013;16: syndrome. BMC Medical Genetics.2011;12:125. 700-704. [52] Dauwerse JG, Dixon J, Seland S, et al.Mutations in genes [34] Mori-Akiyama Y, Akiyama H, Rowitch DH, et al.Sox9 is encoding subunits of RNA polymerases I and III cause required for determination of the chondrogenic cell lineage in Treacher Collins syndrome.Nature Genetics.2011;43:20-22. ƄἛČƚۘऺẟʉ[J].ę the cranial neural crest.Proc Natl Acad Sci USA. 2003;100: [53] ̜,তÒę.Treacher CollinsවȌǍ 9360-9365. ̲Ŀƚ:ἛČƚ ,2005,28(1):46-49,59. [35] Kist R,Schrewe H, Balling R, et al.Conditional inactivation of [54] Khabbaze Y, Karayalcin G, Paley C, et al.Thrombocytopenia Sox9: a mouse model for campomelic dysplasia.Genesis. absent corpus callosum syndrome: Third case of a distinct 2002;32:121-123. clinical entity. J Pediatr Hematol Oncol 2001;23:469-471. [36] Eames BF, Sharpe PT, Helms JA.Hierarchy revealed in the [55] Izumi K, Brooks SS, Feret HA, et al.1.9Mb microdeletion of specification of three skeletal fates by Sox9 and Runx2. Biol. 21q22.11 within Braddock–Carey contiguous gene deletion 2004;274:188-200. syndrome region: Dissecting the Phenotype. Am J Med Genet. [37] Akiyama H, Lyons JP,Mori-Akiyama Y,et al.Interactions 2012;158A:1535-1541. between Sox9 and beta-catenin control chondrocyte [56] Ali Rashidi-NezhadNima Parvaneh,Farideh Farzanfar, Cyrus differentiation. Genes.2004;18:1072-1087. Azimi,et al.2q34-qter duplication and 4q34.2-qter deletion in a [38] Fukami M, Tsuchiya T, Takada S,et al.Complex genomic patient with developmental delay. Eur J Med Genet. 2012; rearrangement in the SOX9 5' region in a patient with Pierre 55(3):203-210. Robin sequence and hypoplastic left scapula.Am J Med [57] Sahoo T, Theisen A, Sanchez-Lara PA, et al. Microdeletion Genet A.2012;158A(7):1529-1534. 20p12.3 Involving BMP2 Contributes to Syndromic Forms of [39] Yamashiro T, Wang XP, Li Z, et al.Possible roles of Runx1 and Cleft Palate. Am J Med Genet A. 2011;155A(7):1646-1653. Sox9 in incipient intramembranous ossification. J Bone Miner [58] Bhoj E,Halbach S,McDonald-McGinn D,et al.Expanding the Res.2004;19:1671-1677. spectrum of microdeletion 4q21 syndrome: A partial [40] Nie X.Sox9 mRNA expression in the developing palate and phenotype with incomplete deletion of the minimal critical craniofacial muscles and skeletons.Acta Odontol Scand. 2006; region and a new association with cleft palate and pierre robin 64:97-103. sequence.Am J Med Genet.2013;161A:2327-2333. [41] Jongsma HJ, Wilders R. Channelopathies: Kir2.1 mutations jeopardize many cell functions. Curr Biol.2001;11:747-750.
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