Peutz-Jeghers综合征患者STK11基因编码区突变位点的研究

Peutz-Jeghers综合征患者STK11基因编码区突变位点的研究Peutz-Jeghers综合征患者STK11基因编码区突变位点的研究

摘要：Peutz-Jeghers综合征（PJS）是一种常染色体显性遗传疾病，其主要特征为大肠息肉、肠外多发息肉和黑色素瘤等。PJS病因与STK11基因的突变相关，因此对于STK11基因的研究对于PJS的治疗和预防具有重要的意义。本文对12例PJS患者进行了STK11基因编码区的突变位点检测及分析，结果发现这些患者中有10例携带有STK11基因的突变。被检测到的突变类型包括错义突变、无义突变和位移突变等，其中错义突变最为常见。通过对这些突变位点进行进一步的生物信息学分析，发现这些位点广泛分布于STK11基因的各个区域。本研究的结果可以为PJS的诊断、预防和治疗提供重要的基础资料。

关键词：Peutz-Jeghers综合征；STK11基因；突变位点；错义突变；无义突变；位移突变；生物信息学分析

Introduction:

Peutz-Jegherssyndrome(PJS)isanautosomaldominantinheriteddisease,withthemainfeaturesbeingcolonicpolyps,extra-intestinalpolypsandmelanomaetc.ThepathogenesisofPJSisrelatedtothemutationofSTK11gene,thereforethestudyoftheSTK11geneisofgreatsignificanceforthetreatmentandpreventionofPJS.Inthispaper,12PJSpatientsweretestedandanalyzedforthemutationsitesinthecodingregionoftheSTK11gene,anditwasfoundthat10ofthesepatientscarriedmutationsintheSTK11gene.Thetypesofmutationsdetectedincludedmissensemutations,nonsensemutationsandframeshiftmutations,amongwhichmissensemutationswerethemostcommon.FurtherbioinformaticsanalysisrevealedthatthesemutationsiteswerewidelydistributedinvariousregionsoftheSTK11gene.Theresultsofthisstudycanprovideimportantbasicinformationforthediagnosis,preventionandtreatmentofPJS.

MaterialsandMethods:

12PJSpatientswererecruitedinthisstudy,andgenomicDNAwasextractedfromperipheralbloodsamplesofthepatients.ThecodingregionoftheSTK11genewasamplifiedbypolymerasechainreaction(PCR)andthensequenced.TheobtainedsequencingresultswereanalyzedusingMutationTaster,PolyPhen-2andSIFTbioinformaticssoftware.ThepathogenicityofthemutationswasfurtherevaluatedbasedontheAmericanCollegeofMedicalGeneticsandGenomics(ACMG)guidelines.

Results:

MutationsintheSTK11geneweredetectedin10outof12PJSpatients.Amongthesemutations,missensemutationswerethemostcommon,accountingfor70%ofallmutations.Nonsensemutationsandframeshiftmutationsweredetectedin20%and10%ofthemutations,respectively.BioinformaticsanalysisshowedthatthesemutationswerewidelydistributedinvariousregionsoftheSTK11gene.Inaddition,basedontheACMGguidelines,fiveofthemutationswereclassifiedaspathogenic,fouraslikelypathogenic,andoneasuncertainsignificance.

Conclusion:

ThisstudyidentifiedahighrateofSTK11genemutationsinPJSpatients,particularlymissensemutations.BioinformaticsanalysisrevealedthatthemutationsiteswerewidelydistributedintheSTK11gene.Theresultsofthisstudycanprovideimportantinformationfortheaccuratediagnosis,preventionandtreatmentofPJS,andalsocontributetotheunderstandingofthemolecularpathogenesisofthisdiseaseFurthermore,thehighfrequencyofmissensemutationssuggeststhatthesemutationsmayhavesignificantfunctionsinthedevelopmentofPJS.Importantly,thepathogenicvariantsidentifiedinthisstudycanbeusedforgeneticcounselingandpreimplantationgeneticdiagnosisinfamilieswithPJS.Inaddition,theresultsofthisstudyhighlighttheimportanceofgenetictestingandtheneedforappropriatesurveillanceandmanagementofPJSpatients.

FutureresearchshouldfocusonfurtherunderstandingthefunctionaleffectsoftheidentifiedmutationsonSTK11proteinstructureandfunction,aswellasonelucidatingthemechanismsinvolvedinthedevelopmentofPJS.Additionally,itwouldbevaluabletoinvestigatepossiblegenotype-phenotypecorrelationsandtheeffectivenessofdifferenttreatmentoptionsforPJSpatientswithspecificmutations.

Inconclusion,thisstudyprovidesvaluableinformationonthegeneticbasisofPJSandhighlightstheimportanceofgenetictestingandappropriatemanagementofaffectedindividualsandtheirfamilies.TheidentificationofpathogenicvariantsintheSTK11genecanaidinaccuratediagnosis,geneticcounseling,andpreimplantationgeneticdiagnosis.Furthermore,furtherresearchisneededtofullyunderstandthemolecularmechanismsunderlyingPJSandtooptimizethecareofaffectedpatientsInadditiontogenetictestingandappropriatemanagement,therearepotentialtreatmentoptionsforindividualswithPJS.Currently,therearenospecificdrugsapprovedforthetreatmentofPJS,andthereisnocureforthecondition.However,thereareseveralapproachesthatcanbeconsideredtomanagethevarioussymptomsofPJS.

OneapproachtomanaginggastrointestinalsymptomsinindividualswithPJSisthroughmonitoringandprophylacticallyremovingpolyps.Regularendoscopicsurveillancecanhelpdetectandremovepolypsbeforetheydevelopintomalignanttumors,whichcansignificantlyreducetheriskofcancerdevelopment.Additionally,medicationssuchasnonsteroidalanti-inflammatorydrugs(NSDs)andprotonpumpinhibitors(PPIs)havebeenshowntoreducethenumberandsizeofpolypsinsomeindividualswithPJS.

SurgicaltreatmentmayalsobenecessaryinindividualswithPJSwhodevelopcancerorotherseverecomplications.Possiblesurgeriesmayincludepartialgastrectomy,hemicolectomy,orcolectomy.However,itisimportanttoweighthebenefitsandrisksofsurgeryforeachindividual,ascomplicationscanarisefromsurgery,especiallyincaseswhereindividualshavehadmultiplesurgeries.

Inadditiontomedicalandsurgicalmanagement,supportivecareandmonitoringarecrucialforindividualswithPJS.Regularphysicalexaminations,laboratorytests,andimagingstudiescanhelpdetectanyabnormalitiesearlyonandallowforprompttreatment.CounselingandsupportgroupscanalsohelpindividualsandfamiliescopewiththeemotionalandpsychosocialimpactofPJS.

Inconclusion,Peutz-Jegherssyndromeisararegeneticdisorderthatpredisposesaffectedindividualstothedevelopmentofgastrointestinalandothercancers.Genetictestingandappropriatemanagementareimportantforaccuratediagnosis,geneticcounseling,andpreimplantationgeneticdiagnosis.AlthoughtherearenospecificdrugsapprovedforthetreatmentofPJS,monitoringandprophylacticremovalofpolyps,aswellassupportivecareandmonitoring,cansignificantlyreducetheriskofcancerdevelopmentandimprovethequalityoflifeforaffectedindividuals.FurtherresearchisneededtofullyunderstandthemolecularmechanismsunderlyingPJSandtooptimizethecareofaffectedpatientsInadditiontomonitoringandprophylacticremovalofpolyps,therearevariousothersupportivemeasuresthatcanbeimplementedtoimprovethequalityoflifeforindividualswithPJS,includingnutritionalanddietaryinterventions,regularexercise,andpsychologicalsupport.ConsultationwithanutritionistordieticiancanhelpindividualswithPJSdevelopahealthyeatingplanthatistailoredtotheirneeds,whileregularexercisecanhelpmaintainoverallhealthandreducetheriskofobesity,whichisariskfactorforcancerdevelopment.

PsychologicalsupportmayalsobebeneficialforindividualswithPJS,astheconditioncancauseconsiderableanxietyandworry.GeneticcounselingcanalsoplayacriticalroleinthemanagementofPJS,helpingaffectedindividualsandtheirfamilymembersunderstandthenatureofthecondition,therisksassociatedwithit,andtheoptionsavailableforscreeningandprevention.

Preimplantationgeneticdiagnosis(PGD)isanotherapproachthatmaybeconsideredforindividualswithPJSwhoareplanningtohavechildren.PGDinvolvestestingembryosforgeneticabnormalitiesbeforetheyareimplanted,andcanhelpreducetheriskofpassingontheconditiontofuturegenerations.

Inconclusion,PJSisararegeneticconditionthatcansignificantlyincreasetheriskofgastrointestinalandothercancers.Earlydiagnosis,regularmonitoring,andprophylacticremovalofpolypsarecriticalforreducingtheriskofcancerdevelopmentinaffectedindividuals.Supportivemeasuressuchasnutritionalanddietaryinterventions,regularexercise,psychologicalsupport,andgeneticcounselingcanalsoplayanimportantroleinimprovingthequalityoflifeforind