Rare Genetic Diseases - National Human Genome Research ...

Around 350 million people on earth are living with rare disorders - this is a disorder or condition with fewer than 200,000 people diagnosed. Skiptomaincontent RareGeneticDiseases Genomicsisendingdiagnosticodysseysforpatientswithrarediseases. Introduction Didyouknowthattherearetrulyrarepeoplebornallthetime?Around350millionpeopleoneartharelivingwithraredisorders-thisisadisorderorconditionwithfewerthan200,000peoplediagnosed.About80percentoftheseraredisordersaregeneticinorigin,and95percentofthemdonothaveevenonetreatment approvedbytheFDA. Theabilitytoreadthehumangenomequicklyandcheaplyhasledtosubstantialadvancesindiscoveringthecausesofraredisorders.Manyfamilieshavegonethroughyearsof"diagnosticodysseys,"goingfromonespecialisttoanothertryingtofindtherootcausefortheirfamilymember'sraredisorder.Itisdifficulttooverstatethereliefthatgenomictestinghasbroughttomanyofthesepatientsandfamilies,notjustforthemselvesbuteventuallyforotheraffectedfamilieswhoarefinallyabletoconnectandsharetheirchallenges.Inthelast10years,alargenumberofpatientgroupshaveformedafterthegenomiccausehasbeenidentifiedforaspecificraredisorder.Thesegroupsallowfamilymembersandpatientstocommunicatewitheachotherthroughsocialmediaorconferences.Perhapsmoreimportantly,manyofthesepatientgroupsareacceleratingresearchonrarediseasesbyrecruitingpatientswiththesameconditiontoparticipateinscientificstudies.Whenfamiliesbandtogether,theireffortssometimesshrinkthepathforestablishingthegeneticbasisforarareconditionfromdecades(andunfortunatelymanypatientlifetimes)toayearortwo. Introduction Didyouknowthattherearetrulyrarepeoplebornallthetime?Around350millionpeopleoneartharelivingwithraredisorders-thisisadisorderorconditionwithfewerthan200,000peoplediagnosed.About80percentoftheseraredisordersaregeneticinorigin,and95percentofthemdonothaveevenonetreatment approvedbytheFDA. Theabilitytoreadthehumangenomequicklyandcheaplyhasledtosubstantialadvancesindiscoveringthecausesofraredisorders.Manyfamilieshavegonethroughyearsof"diagnosticodysseys,"goingfromonespecialisttoanothertryingtofindtherootcausefortheirfamilymember'sraredisorder.Itisdifficulttooverstatethereliefthatgenomictestinghasbroughttomanyofthesepatientsandfamilies,notjustforthemselvesbuteventuallyforotheraffectedfamilieswhoarefinallyabletoconnectandsharetheirchallenges.Inthelast10years,alargenumberofpatientgroupshaveformedafterthegenomiccausehasbeenidentifiedforaspecificraredisorder.Thesegroupsallowfamilymembersandpatientstocommunicatewitheachotherthroughsocialmediaorconferences.Perhapsmoreimportantly,manyofthesepatientgroupsareacceleratingresearchonrarediseasesbyrecruitingpatientswiththesameconditiontoparticipateinscientificstudies.Whenfamiliesbandtogether,theireffortssometimesshrinkthepathforestablishingthegeneticbasisforarareconditionfromdecades(andunfortunatelymanypatientlifetimes)toayearortwo. Bertrand'sStory:FamiliesBandingTogether MattMightandhisfamilyprovideonesuchgenomesequencingstory.MattandhiswifeCristinaknewalmostrightawaythattheirsonBertrandhadsomedifficulties,whichbecameworseovertime.Theyobtained testingforanumberofknowngeneticconditions,butBertranddidnothaveanyofthem.In2010,theyenrolledinastudyatDukeUniversitythatusedDNAsequencingtohelpchildrenwithundiagnoseddisorders.Ittookoverayear,buttheyfinallylearnedthatBertrandhadamutationineachcopyofagenecalled NGLY1. Bertrand'smutationsmeantthathehadnofunctioningcopyofthisgene,andthereforenoN-glycanase1protein(whichthegeneencodes).Hisdisorderwassorarethatmutationsinthisgenehadneverbeendocumented,andhewasthefirstknownhumantolackthisprotein.So,hehelpeddefinethelistofsymptomsobservedwhensomeonedoesnothavetheNGLY1protein,includinganinabilitytoproducetearsorproperlymovesomemuscles.KnowingBertrand'ssymptomsandmutationsquicklyallowedfortheidentificationofatleast15otherchildrenwiththesamedisease,andtheestablishmentofthe NGLY1Foundation tosupportresearchaboutthediseaseandpursuepossibletreatments.In2015,MattwasoneofthoseinvitedtotheWhiteHousebyPresidentObamatocelebratetheannouncementofthePrecisionMedicineInitiative. Bertrand'sStory:FamiliesBandingTogether MattMightandhisfamilyprovideonesuchgenomesequencingstory.MattandhiswifeCristinaknewalmostrightawaythattheirsonBertrandhadsomedifficulties,whichbecameworseovertime.Theyobtained testingforanumberofknowngeneticconditions,butBertranddidnothaveanyofthem.In2010,theyenrolledinastudyatDukeUniversitythatusedDNAsequencingtohelpchildrenwithundiagnoseddisorders.Ittookoverayear,buttheyfinallylearnedthatBertrandhadamutationineachcopyofagenecalled NGLY1. Bertrand'smutationsmeantthathehadnofunctioningcopyofthisgene,andthereforenoN-glycanase1protein(whichthegeneencodes).Hisdisorderwassorarethatmutationsinthisgenehadneverbeendocumented,andhewasthefirstknownhumantolackthisprotein.So,hehelpeddefinethelistofsymptomsobservedwhensomeonedoesnothavetheNGLY1protein,includinganinabilitytoproducetearsorproperlymovesomemuscles.KnowingBertrand'ssymptomsandmutationsquicklyallowedfortheidentificationofatleast15otherchildrenwiththesamedisease,andtheestablishmentofthe NGLY1Foundation tosupportresearchaboutthediseaseandpursuepossibletreatments.In2015,MattwasoneofthoseinvitedtotheWhiteHousebyPresidentObamatocelebratetheannouncementofthePrecisionMedicineInitiative. Sonia'sStory:LookingforaTreatment Anotherinspiringstoryofhowgenomesequencingcantransformthelifeofsomeonewithararediseasecomesfrom SoniaVallabhandEricMinikel.Afterararediseasetookhermother'slife,theylearnedthroughgenetictestingthatSoniahadinheritedthesamemutationthatcauses familialfatalinsomnia,orFFI.Thisfataldisease,causedbyabnormalproteinsinthebraincalledprions,makesthebrainstartfunctioningabnormally,withsymptomsthateventuallyincludeatotalinabilitytofallasleep.SoniaandEricquittheirjobsandcareerstogobacktograduateschoolinbiomedicine,andareearningtheirdoctoraldegreesfromHarvardMedicalSchoolbystudyingthemutationsinthe PRNP genethatcause priondiseaseslikeFFI. Alongwiththeircolleagues,thecouplehavealreadyconductedagroundbreakingstudyontheimpactof PRNP mutations.Wealreadyknewthatdifferent PRNP mutationsleadtodifferentconditionsbasedonwhereinthegenethemutationislocated.However,EricandSonia'steammadethesurprisingdiscoverythat PRNP mutationsaremorecommonthanwepreviouslythought,and thesemutationsdon'tseemtocausediseaseatthesamerateineveryonewhohasthem.Inotherwords,therearestillfactorswedon'tunderstandthatdeterminewhetherornota PRNP mutationwillleadtocertainsymptoms.Thisinformationopensupmorequestions,butitalsopointstoimportantdirectionsforanyfuturestudiesofthisandotherrarediseases. Sonia'sStory:LookingforaTreatment Anotherinspiringstoryofhowgenomesequencingcantransformthelifeofsomeonewithararediseasecomesfrom SoniaVallabhandEricMinikel.Afterararediseasetookhermother'slife,theylearnedthroughgenetictestingthatSoniahadinheritedthesamemutationthatcauses familialfatalinsomnia,orFFI.Thisfataldisease,causedbyabnormalproteinsinthebraincalledprions,makesthebrainstartfunctioningabnormally,withsymptomsthateventuallyincludeatotalinabilitytofallasleep.SoniaandEricquittheirjobsandcareerstogobacktograduateschoolinbiomedicine,andareearningtheirdoctoraldegreesfromHarvardMedicalSchoolbystudyingthemutationsinthe PRNP genethatcause priondiseaseslikeFFI. Alongwiththeircolleagues,thecouplehavealreadyconductedagroundbreakingstudyontheimpactof PRNP mutations.Wealreadyknewthatdifferent PRNP mutationsleadtodifferentconditionsbasedonwhereinthegenethemutationislocated.However,EricandSonia'steammadethesurprisingdiscoverythat PRNP mutationsaremorecommonthanwepreviouslythought,and thesemutationsdon'tseemtocausediseaseatthesamerateineveryonewhohasthem.Inotherwords,therearestillfactorswedon'tunderstandthatdeterminewhetherornota PRNP mutationwillleadtocertainsymptoms.Thisinformationopensupmorequestions,butitalsopointstoimportantdirectionsforanyfuturestudiesofthisandotherrarediseases. ScienceForEveryone Ifyouhaveafamilymemberwhohasseenanumberofmedicalprofessionalsbutnotyetreceivedadiagnosis,theycouldapplytothe NIH'sUndiagnosedDiseaseNetwork.Thisnationalnetworkofmedicalandresearchcentersaimstohelpbothindividualpatientsandtocontributetotheunderstandingofhowthehumanbodyworks.That'swhatZarkoStanacevdid-after12yearsofmysterioussymptomsbutnodiagnosis,hisgenomewassequencedandinterpretedbyateamincludingDr.WilliamGahlattheU.S.NationalInstitutesofHealth.Theyfoundamutationinthegene NLRP3, whichcausesabnormalinflammationthroughoutthebody.Afteronlyonetreatmentwithamedicinetodampenthisinflammation,Zarko'ssymptomsimproved. JustlikeSoniaandBertrand,hehascontributedtomedicalresearchbyallowinghisgenometobesequencedandstudied. AdditionalResources: ScienceDidn'tUnderstandMyKids'RareDiseaseUntilIDecidedtoStudyIt:SharonTerry,TEDMed2016 HudsonAlphaInstituteforBiotechnology-TheCSERProgram:Tiana'sStory ThePEARLSProject:PositiveExposureAmbassadors'RealLifeStories RareActionNetworkStateActionCenter NIH-GeneticandRareDiseasesInformationCenter ResourcesforEducators CareerProfile: GeneticNurse | Video CareerProfile: PhysicianAssistant | Video PBS/WETA-TheGeneDoctorsVideos AmericanSocietyofHumanGenetics-RareDiseaseDiagnosisThroughSequencing&BioinformaticsHands-OnActivity NIH-GeneticsHomeReference ResourcesforHealthcareProviders NIH-GeneticandRareDiseasesInformationCenter NIH- UndiagnosedDiseaseNetwork(UDN) AmericanCollegeofMedicalGeneticsandGenomics:FindGeneticServiceProviders NLMMedGen-DetailedInformationonHumanMedicalGeneticsConditions NLM GeneReviews-ClinicallyRelevantandMedicallyActionableInformationforInheritedConditions:E-Book AmericanSocietyofHumanGenetics-RareDiseasesInfographic ScienceForEveryone Ifyouhaveafamilymemberwhohasseenanumberofmedicalprofessionalsbutnotyetreceivedadiagnosis,theycouldapplytothe NIH'sUndiagnosedDiseaseNetwork.Thisnationalnetworkofmedicalandresearchcentersaimstohelpbothindividualpatientsandtocontributetotheunderstandingofhowthehumanbodyworks.That'swhatZarkoStanacevdid-after12yearsofmysterioussymptomsbutnodiagnosis,hisgenomewassequencedandinterpretedbyateamincludingDr.WilliamGahlattheU.S.NationalInstitutesofHealth.Theyfoundamutationinthegene NLRP3, whichcausesabnormalinflammationthroughoutthebody.Afteronlyonetreatmentwithamedicinetodampenthisinflammation,Zarko'ssymptomsimproved. JustlikeSoniaandBertrand,hehascontributedtomedicalresearchbyallowinghisgenometobesequencedandstudied. AdditionalResources: ScienceDidn'tUnderstandMyKids'RareDiseaseUntilIDecidedtoStudyIt:SharonTerry,TEDMed2016 HudsonAlphaInstituteforBiotechnology-TheCSERProgram:Tiana'sStory ThePEARLSProject:PositiveExposureAmbassadors'RealLifeStories RareActionNetworkStateActionCenter NIH-GeneticandRareDiseasesInformationCenter ResourcesforEducators CareerProfile: GeneticNurse | Video CareerProfile: PhysicianAssistant | Video PBS/WETA-TheGeneDoctorsVideos AmericanSocietyofHumanGenetics-RareDiseaseDiagnosisThroughSequencing&BioinformaticsHands-OnActivity NIH-GeneticsHomeReference ResourcesforHealthcareProviders NIH-GeneticandRareDiseasesInformationCenter NIH- UndiagnosedDiseaseNetwork(UDN) AmericanCollegeofMedicalGeneticsandGenomics:FindGeneticServiceProviders NLMMedGen-DetailedInformationonHumanMedicalGeneticsConditions NLM GeneReviews-ClinicallyRelevantandMedicallyActionableInformationforInheritedConditions:E-Book AmericanSocietyofHumanGenetics-RareDiseasesInfographic Lastupdated:April13,2018