sign in sign up
<<
Home , Gonadal dysgenesis, Polysomy, Tetrasomy, Turner syndrome, XXYY syndrome, XYY syndrome

Guilherme Guaragna-FilhoGuilherme Aparecida Siviero-Miachon Arq Bras Metab. Endocrinol 2012;56/8 deumaaneuploidia decromossomossexuais. sugestivo a análise citogenética clássica traz resultados normais ou incertos em pacientes com quadro pela linhagem48,XXYY. OusodeFISHnapráticaclínicaéparticularmente relevantequando na avaliaçãoeconduçãodos casos.Nocaso3,afunçãogonadalanormalpôdeserexplicada variabilidade fenotípicadomosaico 45,X/46,XYeaimportância da detecçãodalinhagem45,X linfócitos e mucosa oral identificou a constituição 47,XYY/48,XXYY. Os casos 1 e 2 ilustram a lógicos, altaestatura,testículospequenos,gonadotrofinas elevadas eazoospermia. FISH de com atrasodedesenvolvimento neuromotor, dificuldadedeaprendizado, problemaspsico levando aodiagnósticodedisgenesiagonadalmista.Ocaso 3éumrapazde19 anos,47,XYY, disgenética àesquerda).FISHdelinfócitosemucosaoralidentificou ocariótipo45,X/46,XY, de 21meses,46,XY, comambiguidadegenital(hipospadia peniana,testículoàdireitaegônada ção 45,X/46,X,idic(Y)eestabeleceuodiagnósticodesíndrome de Turner. Ocaso2éummenino tura. A análisedelinfócitosporFISHcomsondascentroméricasXe Y identificouaconstitui anos, 46,XY, comgenitáliafemininanormal,encaminhada aonossosetordevidoàbaixaesta casos nosquaisodiagnósticofinalsófoiobtidopormeiode FISH.Ocaso1éumameninade8 destetrabalhoédescrevertrês saicismo emanomaliasdecromossomossexuais.Oobjetivo FISH temsidousadocomoumcomplementoparaacitogenética clássicanadetecçãodemo SUMÁRIO patients withfeaturesofsexchromosome . is particularly relevant when classical cytogenetic analysis yields normal or uncertain results in gonadal functioncouldbeexplainedbythe48,XXYYcellline. The useofFISHinclinicalpractice tance ofdetectionthe45,Xcelllineforpropermanagementandfollow-up. Incase3,abnormal Cases 1and2illustratethephenotypicvariabilityof45,X/46,XYmosaicism,impor mia. FISHanalysisoflymphocytesandbuccalsmearidentifieda47,XYY/48,XXYY constitution. ties, psychological problems,tallstature,smalltestes,elevatedgonadotropins, andazoosper Case 3was a47,XYY 19-year-old boywithdelayedneuromotordevelopment,learningdisabili , leadingtodiagnosisofmixedgonadaldysgenesis. cal smearidentifieda45,X/46,XY (penile hypospadias, righttestis,andleft streakgonad).FISHanalysisoflymphocytesandbuc the diagnosis of Turner . Case 2 was a 21-month-old 46,XY boy with genital ambiguity probes fortheXand Y centromeresidentifieda45,X/46,X,idic(Y)constitution,andestablished male genitaliareferred toourservicebecauseofshort stature.FISHanalysis oflymphocyteswith diagnosis could only be achieved by FISH. Case 1 was an 8-year-old 46,XY with normal fe anomalies. The aimofthisstudyistodescribethreecasesinwhich thefinal FISH hasbeenusedasacomplementtoclassicalcytogeneticsinthedetectionofmosaicism SUMMARY Andréa TrevasMaciel-Guerra casos deanomaliascromossomos sexuais diagnóstico demosaicismooculto: apropósito detrês insitu com fluorescênciaO usodahibridação no cases ofsex chromosome anomalies hidden mosaicism: apropos ofthree hybridization inthediagnosisof The useoffluorescence insitu 3 4 , Juliana Ribeiro Gabriel Andrade , Spinola-CastroÂngela Maria 1,2 , Juliana DePaulo Arq BrasEndocrinolMetab. 2012;56(8):545-51 Arq BrasEndocrinolMetab. 2012;56(8):545-51 1 , Ana Paula Santos 4 , GilGuerra-Júnior 1,2 , Adriana 1 , 2,3 ------

de Campinas Médicas, Universidade Estadual Médica, Faculdade deCiências EPM), SãoPaulo, SP, Brazil Federal deSãoPaulo (Unifesp- de Medicina,Universidade Pediátrica, EscolaPaulista Unidade deEndocrinologia Campinas, SP, Brazil Pediátrica, FCM-Unicamp, Unidade deEndocrinologia Unicamp, Campinas,SP, Brazil do Sexo (GIEDDS),FCM- da DeterminaçãoeDiferenciação 1 Accepted onOct/4/2012 Received onJuly/31/2012 [email protected] 13083-887 –Campinas, SP, Brazil Médica, FCM-Unicamp deGenética Departamento Andréa TrevasMaciel-Guerra Correspondence to: 4 3 2 Campinas, SP, Brazil Departamento deGenética Departamento Departamento dePediatria,Departamento dePediatria,Departamento Grupo InterdisciplinardeEstudos

case report

(FCM-Unicamp), 545

Copyright© ABE&M todos os direitos reservados. Copyright© ABE&M todos os direitos reservados. 546 + =present;-absent; CV=cardiovascular;DVTdeepveinthrombosis; F=;Mmales. Table 1. Mainfeaturesofnumericalsexchromosomeanomalies or cell lineandasecondcontainingnormal and 45,X/46,idic(Y)(8,9).Mosaicismwitha45,X e.g.,45,X/46,XY;45,X/47,XYY; in thekaryotype, Ychromosome abnormal orstructurally have normal inTS,whichabout5%of thecasesmay larly true inavarietyofcombinations.This isparticu present mosomes (2-7)(Table 1). sexchro thanthree inpolysomieswithmore features alsofrequent are deficiency andbehavioralproblems ism and(or)multiplecongenitalanomalies;mental hypogonad primary disorders, usually includegrowth andotherpolysomies,theclinicalpicture in have few ornophysical developmental problems, may individuals witha47,XXXor47,XYYkaryotype constitutions) (2).While and 49,XXXXY chromosome cases of48,XXXX;48,XXXY;48,XXYY; 49,XXXXX; 47,XXX;47,XYYandrare or Klinefeltersyndrome; (45,X orTurner andpolysomies(47,XXY syndrome) tural ornumerical,andthelattercomprisemonosomy S INTRODUCTION Molecular andhiddenmosaicism overall incidenceof1:448(1).Theycanbeeitherstruc 48,XXYY 48,XXYY 48,XXXY 49,XXXXX 48,XXXX 47,XXX 49,XXXXY 47,XYY 47,XXY 45,X Karyotype Mosaicism in anomaliescanbe Mosaicism insexchromosome chromosome abnormalities in newborns, withan innewborns, abnormalities chromosome themostfrequent osome anomaliesare ex chrom 1:100,000 M 1:40,000 M 1:50,000 M Incidence 1:18,000- 1:85,000- 1:2,130 F 1:851 M 1:576 M 1:897 F ? Greater frequency Greater frequency Greater frequency Greater frequency Greater frequency Greater frequency with normalmen with normalmen when compared when compared when compared when compared when compared when compared retardation with normal with normal Mental women + + + + - Greater frequency Greater frequency Greater frequency Greater frequency Greater frequency Greater frequency with normalmen with normalmen when compared when compared when compared when compared when compared when compared Behavioral with normal with normal disorders Variable women + + + - Stature Short Short Short Tall Tall Tall Tall Tall - - - - , including streak gonadsandfemalegeni phenotypes, includingstreak abnormal particularly relevant when classical cytogenetic analy relevant particularly for thediagnosisofhiddenmosaicism(15).Thisis test as a quick and reliable cells has also been proposed of mosaicism(13,14).Moreover, thestudyofmucosa specificandsensitive detection (12), andforamore fortheidentificationofmarkerchromosomes FISH analysishasbeenacomplementtoclassicalcyto phase cellnuclei(11). and(or)inter preparations andcanbeappliedto abnormalities, of chromosome as avaluabletoolfortheidentificationanddefinition mosomes. It has been incorporated toclinical practice ence or absence of specific DNA sequencesonchro genetic techniqueusedtodetectandlocalizethepres phenotypes (2). may leadtointermediate and(or) polisomiccelllines, ing monosomic,normal anomalies, includ Other mosaics of sex chromosome may have anomalies characteristic of TS (10). virilized malewithinfertility. Inaddition,thesepatients talia, dysgenetictestesandsexambiguity, andnormal results inpatientswith results oruncertain sis bringsnormal premature ovarianfailure Unknown frequency of Unknown frequencyof Gonadal function Within the group of , ofsexchromosome thegroup Within Fluorescence Hypergonadotropic Hypergonadotropic Hypergonadotropic Hypergonadotropic Hypergonadotropic Hypergonadotropic Hypergonadotropic Hypergonadotropic Hypergonadotropic Hypergonadotropic Hypergonadotropic Usually normal Usually normal hypogonadism hypogonadism hypogonadism hypogonadism hypogonadism leads to a wide spectrum of leadstoawidespectrum Y chromosome in situhybridization(FISH)isacyto anomalies, typeIIdiabetes, seizures, anomalies, typeIIdiabetes, seizures, anomalies, typeIIdiabetes, seizures, Dysmorphic picture, CVanomalies anomalies, autoimmunedisorders Dysmorphic picture, CVandrenal Dysmorphic picture, CVandrenal Dysmorphic picture, CVandrenal Dysmorphic picture, CVandrenal Additional medicalproblems Minor physicalfindings, varicose low frequency of genitourinary low frequencyofgenitourinary veins, DVT, diabetesmellitus , Congenital anomalies/ Minor physicalfindings, anomalies andseizures Minor physicalfindings autoimmune disorders Arq Bras Metab. Endocrinol 2012;56/8 DVT DVT DVT 1, 2,6 3,6,7 1,2,6 1,2,6 4,6,7 4,6,7 6,16 Ref. 1,2 ------Arq Bras Metab. Endocrinol 2012;56/8 healthyandnonconsanguineous parents from term camp) becauseofgenitalambiguity. at Hewasborn Hospital ofUniversidadeEstadual deCampinas(Uni totheUniversity This 21-month-oldboywas referred 2 Case wasestablished. drome as 45,X/46,X,idic(Y), and the diagnosis of Turner syn ofthegirlwasdefined mosome. Thus,thekaryotype and interphasenuclei,indicatinganisodicentricYchro both in metaphase chromosomes probe Y the signalsfrom twored were ble 2).Inaddition,there 1Aand1B,Tamosaicism witha45,Xcellline(Figures which identified (DXZ1) and Y (DYZ3) , fortheX lymphocytes usingthealpha-satelliteprobes plete XYgonadaldysgenesis,ledtoFISHanalysisof , whichcouldenable the diagnosis of com and TS stigmata, together with the absence of beganwhenshewas12yearsold. with femalehormones therapy replacement . streak revealed bilateralgonadectomy,underwent andhistopathology cing oftheSRY pelvic region. andgonadslocatedinthe hypoplasticuterus, revealed tor axis – hormone and thegrowth function anomalies; thyroid orrenal no cardiovascular were typicallyfemale.There genitaliawere External nails. andhyperconvex neck, ,genuvarum, webbed palate,micrognathia, thic folds,high-arched stigmata: lowposteriorhairline,low-setears,epican someTurner were low themean,andthere syndrome deviations be examination, height was 2.25 standard On physical stature. age of8yearsbecauseshort Universidade FederaldeSãoPaulo(Unifesp)atthe totheUniversityHospitalof This girlwasreferred 1 Case Clinical reports SUBJECTS ANDMETHODS chromosomes. forXand Y be achievedbyFISHwithspecificprobes some anomaliesinwhichthefinaldiagnosiscouldonly casesofsexchromo this studyistodescribethree aneuploidy. ofsexchromosome features Theaimof When the girl was 18 years old, her stature When thegirlwas18yearsold,hershort was46,XY(50cells),andsequen­ Her karyotype were both normal. Ultrasoundexamination bothnormal. were did not show any . She genedidnotshowanymutation.She insulin-like growth fac insulin-likegrowth SRY ------

2,850 g and length 47 cm. He had normal neuromo 2,850 gandlength47cm.Hehadnormal after anuneventfulpregnancy, weightof withbirth below the3 for themalesex. ng/mL, whichisconsistentwiththeexpectedpattern to 1.9 rose of 2000IUonsuccessivedays) intramuscular injections (hCG) stimulation test (three 0.02 ng/mL).Afterahumanchorionicgonadotropin (< mIU/mL), LH(<0.1mIU/L),andtestosterone levelsofFSH(1.05 type (50cells)andprepubertal and theleftonewasnot. spadias. Therightgonadwaspalpable in thescrotum, slightly abovethe3 unremarkable. 6-year-old was had anormal sister, andfamilyhistory ofpainfulurination.He tor developmentandhistory Hospital of Unicamp due to tall stature, smalltestes,Hospital ofUnicamp duetotallstature, totheUniversityA 19-year-old boy was referred 3 Case (MGD). diagnosis waschangedtomixedgonadaldysgenesis wasfoundtobe45,X/46,XYandhis tient’s karyotype 1C,Tablea 45,Xcellline(Figure 2).Thus,thepa and buccalsmearcells,identifiedmosaicismwith wasdonebothinlymphocytes and Ychromosomes kg (z=-1.1). = -2.3;meantarget height:175cm), and weight29.5 lies. Attheageof10.9years,heightwas127.5cm(z anoma anyrenal sound examinationdidnotreveal nootherassociatedconditions,andultra were there duringfollow-up,but pronounced cy becamemore deficien Growth the pediatricendocrinologyservice. innadal dysgenesisandwasfollowedupthereafter . astreak and histopathologyrevealed testis.Theleftgonadwasthenremoved, prepubertal cells,whilebiopsiesoftherightgonadshowed of germ tissuedevoid sies oftheleftgonadshowedonlyfibrous biop Further sue compatiblewithMüllerianremnants. tis of epididimus and uterine tube, and fibromuscular testis,segments prepubertal nad anditsadnexarevealed inguinalring;biopsiesofthisgo ted neartheinternal pair andsurgical exploration.Theleftgonadwasloca­ rotated ears, a 3-cm phallus with chordee, penilehypo ears,a3-cmphalluswith chordee, rotated A few months later, he underwent hypospadiasre A fewmonthslater, heunderwent a46,XYkaryo investigationrevealed Laboratory On physicalexamination,weight(10.1kg)was FISH analysis using centromere probes fortheX probes FISH analysisusingcentromere go The childwasdiagnosedas having XY partial rd percentile. Hehadlow-setandposteriorly percentile. Molecular cytogenetics andhiddenmosaicism rd percentile, andheight(77cm) percentile, 547 ------

Copyright© ABE&M todos os direitos reservados. Copyright© ABE&M todos os direitos reservados. 548 Table 2. DetailsofFISHresultsforeachcase type wasfoundtobe47,XYY/48,XXYY. Lowlevelmo mosaicism witha48,XXYYcellline.Thus,hiskaryo in lymphocytesandbuccalsmearcells,identified wasdoneboth fortheXandYchromosomes probes FISHanalysis using centromere 47,XYY syndrome, isnottypicalofthe andinfertility ism, microrchidia, vealed azoospermia. countre was47,XYY(50cells),andsperm karyotype (16.93and11.00pg/mL;NR 8.8-27.0). His terone testos and 10.65mIU/mL,NR1.7-8.6),normal toelevatedLH(8.30mIU/mL NR, 1.5-12.4),normal malerange, mIU/mL and16.14mIU/mL,normal highlevels ofFSH(17 (19 and19.5years)revealed bic hairwasonTanner stageP5. volume(right:12cm with reduced deviations), andbothtestespalpableinthescrotum with a11.5-cmphallus(slightlyabove-2.0standard typically male, genitalia were necomastia, and external nogy wasnodysmorphicpicture, (z =0.47).There 2.43; meantarget height:176cm),andweight76kg cases inthefamily. nosimilar were consanguineous couple,andthere 11 yearsold.Hewastheyoungeroftwosonsa whenhewas repair ofrightinguinalhernia a history was alsorelationship withhispeers.There ficulties in disabilities,anddif development,learning romotor 2,950 gandlengthof49cm.Hehaddelayedneu weightof withabirth ter anuneventfulpregnancy af atterm Hewasborn and elevatedgonadotropins. Molecular cytogenetics andhiddenmosaicism Buccal cells Blood Blood metaphase Case 3 Buccal cells Blood interphase Blood metaphase Case 2 Blood interphase Blood metaphase Case 1 Parameters As the picture of hypergonadotropic hypogonad ofhypergonadotropic As thepicture occasions investigationintwodifferent Laboratory On physicalexamination,heightwas194cm(z= One Xsignal 234 (23.4) 159 (15.9) 15 (10.4) 27 (13.5) 25 (25) (%) One XandoneY 3 ; left:10cm 766 (76.6) 841 (84.1) 129 (89.6) 20 (4.3) 62 (6.2) signals (%) 3 ). Pu One XandtwoY 131 (28.5) 152 (92.1) 173 (86.5) 890 (89) ------signals 75 (75) (%) (or) buccalsmearswer peripheral blood lymphocytes and interphase cells from phosphate-buffered saline(PBS1X) andPBS 1X sup phosphate-buffered excess keratin and cytoplasm; washed with to remove 0.005% in10mMHClfor40minat37°C(Sigma) 2X SSCfor2minat73°C,andwithpepsin(Sigma) with pretreated hybridization, slides were lows: before on Shoumanandcols.(17)wasmodifiedasfol instructions. tothemanufacturers’ cording Cytocell ogy incase1,andfrom Biotechnol Kreatech from and Y(DYZ3)centromeres fortheX(DXZ1) ples usingthealpha-satelliteprobes onbloodsam performed banding. FISHstudieswere techniquesandG- blood lymphocytesusingstandard onperipheral performed analyseswere Chromosome Cytogenetic andFISHanalyses F, Table 2). 1D- lymphocytesandbuccalsmear(Figures cells from foundininterphase was alsosuggestedbytheresults saicism withtwoothercelllines(46,XYand47,XXY) DAPI (Cytocell counterstainingwith before temperature SSC atroom 0.4X SSC/0.15%Tween 20for2minat73°C, and2X washedwith2XSSCfor5 minat37°C, slides were 100% ethanolfor1minuteeach.Afterhybridization, at 73°C,anddehydratedinwashesof70%,85% SSCfor2min in70%formamide/2X denatured were with 70%,85%and100%ethanolfor1mineach.Slides anddehydrated plemented with37%formaldehyde; A hundred to 165 metaphase cells, and 200 to 2,000 A hundred Our protocol onbuccalsmearsampleswasbased Our protocol Two XandoneY 24 (5.2) signals (%) ® ). e analyzedforeachpatient. Two XandtwoY Arq Bras Metab. Endocrinol 2012;56/8 285 (62) 46 (4.6) signals 13 (7.9) (%) ® incases2and3,ac Total cells 1000 1000 460 998 165 144 200 100 - - - - - Arq Bras Metab. Endocrinol 2012;56/8 may bemutationsin there guity (18).In both disorders, gonadandgenitalambi­ dysgenetic testisandastreak a acterized bythefindingof twodysgenetictestes,or gonadaldysgenesis (XYPGD),char 2, 46,XYpartial genitaliaand,incase andexternal and femaleinternal gonads dysgenesis (XY CGD), characterized by streak in case1,thehypothesisof46,XYcompletegonadal indicated, of a 45,X cell line in theclassical karyotype nosis thatmayarise during investigation. The absence diag the 45,X/46,XYmosaicism,anddifferential tissues. tion, mosaicismmaybeconfinedtoonlyoneorfew sues; whenitoccursinacellafterextensivedifferentia tis may bedetectableinmostcelllinesandresulting thebodyand throughout evenlyspread saicism ismore hasonlyafewcells,mo If itoccurswhentheembryo rearrangement. disjunction, anaphaselag,or structural ofpost-zygotic non- same individual,andistheresult celllinesinthe different karyotypically two ormore of mosaicismisdefinedas thepresence Chromosomal DISCUSSION Original magnificationx1,000. two Xandone Y signals(47,XXY). f) constitution. one Xsignal corresponding to the45,Xcell line, and others onthe left showing one Xand Y signal(46,XY). d)Case3: metaphase cell witha48,XXYY a 45,Xconstitution.b)Case1: metaphasecellwitha46,X,idic(Y)constitution. c)Case2: interphasecellsfrombuccalsmearontheright, showingonly Figure 1. FISHusingDXZ1andDYZ3probesforX Y chromosomescentromeres(greenandredsignals, respectively). a)Case1: metaphasecellwith D A Cases 1 and 2 illustrate the phenotypic variability of Cases 1and2illustratethephenotypicvariabilityof e) Case 3: interphasecellsfrombuccalsmearshowingtwoXand Y signalscorrespondingtothe48,XXYYcellline, andacellshowing Case 3: interphasecellfrombuccalsmearshowingoneXandtwo Y signalscorrespondingtothe47,XYYcellline. B E - - - - - scrotal folds,duetothehighriskofneoplastictransfor scrotal not locatedinthe as welldysgenetictestesthatare gonadsmustberemoved, streak Also, inbothdisorders, inXYPGD). frequent also beunknown(whichismore CGD) or the NR5A1 gene (21,22), but the origin may the partial testicular dysgenesisandgenitalambiguity in partial (24). anomalies andhypothyroidism renal and and associatedconditions, such ascardiovascular ism inmostcases,highlyvariable dysmorphicpicture, hypogonad andprimary stature withshort anddefined clinicallybyafemale ond sexchromosome; absenceofthesec andtotalorpartial , ofan was TS,definedcytogeneticallybythepresence Incase 1, final diagnosis and follow-up of the children. management alsoenablingproper ses tobeconfirmed, TS incase1.TheuseofFISHenabledthesehypothe suggestiveof cases, togetherwithdysmorphicfeatures dicating thepossibilityofhiddenmosaicisminboth (23). mation (gonadoblastomasanddysgerminomas) In case 2, the final diagnosis of MGD was based on In case2,thefinaldiagnosis ofMGDwasbasedon in deficiencywasthemainclinicalfeature Growth SRY gene (19,20) (which are more frequent in XY inXY frequent more gene(19,20)(whichare Molecular cytogenetics andhiddenmosaicism C F 549 ------

Copyright© ABE&M todos os direitos reservados. Copyright© ABE&M todos os direitos reservados. 550 (32). However, FISHanalysiswasdone manyyearsaf mosaicism equalto6%orgreater, with 95%confidence inbothcases enabledtheexclusionof the karyotype ted whenoneconsidersthat theanalysisof50cellsin thanexpec ­ wasgreater 2 (25%and10%,respectively) cell lineinmetaphasesanalyzed byFISHincases1and about worseningofbehaviorwiththistherapy(31). maybeconcerns (7), thoughthere replacement drogen levelsand,ifnecessary,monitoring oftestosterone an not modifythemanagementofthispatient,whoneeds ofKlinefeltersyndrome. physical features and behaviorproblems, mentalretardation, stature, case:tall similar tothepresent of them(29)wasvery of two (29,30);theclinicalpicture found inliterature incase3. was alsoobserved cell linesusuallyvariesamongtissuetypes(28),andthis toabnormal ofnormal somal mosaicismtheproportion this (Table 1).Inindividualswithchromo commonin FISH explainedthesefindings,whichare Thedetectionofthe48,XXYYcelllineby karyotype. notusuallyfoundinindividualswiththis are ospermia hypogonadism,andazo volume, hypergonadotropic constitution.However,this chromosome lowtesticular compatiblewith were in47,XYYsyndrome, frequent thoughin ing disabilitiesandpsychologicalproblems, thus generatingthe45,Xcellline(27). duringmitotic divisions, the lossofYchromosome to ofthegirl.Thisanomalypredisposes karyotypying mosaicism (26),andhadnotbeendescribedinclassical in45,X/46,XY observed centrism), whichisfrequently (di anomalyoftheYchromosome tion ofastructural (25). therapywithtestosterone Leydig cellsmayrequire of failure spontaneous malepuberty, thoughsecondary assignment, maintenanceofatleastonetestismayallow the otherhand,inpatientswithMGDamalesex On whom bilateralgonadectomymustbeperformed. asfemales,in of TS,andinthecasesMGDreared inmostcases necessary are ment, femalehormones replace final height (24,25). Regarding in mayleadtoimprovement hormone use ofgrowth those of TS; in addition, in both TS and MGD, the Thus, managementandfollow-upmustbeidenticalto (25). andTSfeatures with a45,X/46,XYkaryotype, thatofXY PGD, but associated distinguishable from Molecular cytogenetics andhiddenmosaicism It is worth commenting that the proportion of45,X commentingthattheproportion It isworth The findingofthissecondcelllineincase3did Few casesof47,XYY/48,XXYYmosaicismare development, learn In case3,delayedneuromotor The useofFISHincase1alsoenabledthedetec ------the investigation to a different tissue, replacing skinbi tissue,replacing the investigationtoadifferent buccalsmearsmayextend also ininterphasecellsfrom TS,andthattheuseofFISH anomalies, particularly ofsexchromosome feature that mosaicismisafrequent The clinician must keepinmind ones described here. a usefultooltoinvestigateatypicalcases,suchasthe However, FISHis be solvedbyclassicalkaryotyping. anomalies,sincemostcasesmay a sexchromosome issuggestiveof ate individualswhoseclinicalpicture usedinclinicalpracticetoevalu this techniqueisrarely TS canchangedramaticallyovertime(33,34). ofmosaicismin studies haveshownthatthepercentage case2,in vivo ofthe45,Xcellline.Regarding portion pro and thiscontinuouslossmayleadtoanincreasing e during mitotic divisions (27), loss of this chromosom to incase1predisposes anomaly oftheYchromosome pointedout,structural 9 yearsincase2).Asalready inbothcases(10yearscase1,and ter karyotyping 8. 7. 6. 5. 4. 3. 2. 1. REFERENCES was reported. relevant tothisarticle nopotentialconflictofinterest Disclosure: pesp) (2011/50189-7). àPesquisadoEstadodeSãoPaulo(Fa Fundação deAmparo by Estadual deCampinas(Unicamp).Thisstudywassupported ofMedicalGeneticsUniversidade oftheDepartment ratory gratefultotheCytogeneticsLabo Acknowledgments: weare invasive manner(35). reliable, fast,andnon ina culture opsy andfibroblast

Although FISH has been widely used in research, Although FISHhasbeenwidelyusedinresearch, Paulo MedJ. 2009;127(6):373-8. Y chromosome in : reviewof the literature.Sao RM, Oliveira Verreschi IT, LipayMV, Eça LP, Guedes AD, BiancoB. ter syndrome. Acta Paediatr. 2011;100(6):851-60. 48,XXXY and49,XXXXYsyndromes: notjustvariantsofKlinefel- Tartaglia N, Ayari N,HowellS,D’EpagnierC,ZeitlerP. 48,XXYY, aneuploidy. Am JMedGenet A. 2010;152A(5):1206-12. a nonlinearfashion:studyof305patientswithsexchromosome CH, etal.Increasednumberofsexchromosomes affects heightin Ottesen AM, Aksglaede L,GarnI, Tartaglia N, Tassone F, Gravholt chromosome aneuploidy. ObstetGynecol. 1996;87(3):468-75. Linden MG,BenderBG,Robinson A. Intrauterinediagnosisofsex 1988;80(1):16-22. somy inthemale. The Leuven experience1966-1987. HumGenet. Kleczkowska A, Fryns JP, Van denBergheH.X-chromosome poly drome. JMentDefic Res. 1978;22(3):197-205. Sørensen K,NielsenJ, Jacobsen P, Rølle T. The 48,XXYYsyn- Lab Med.2011;31(4):463-79. Li X.Sex chromosomes andsexchromosome abnormalities.Clin 1990;26(4):209-223. dence studyin Arhus, .Birth DefectsOrig Artic Ser. among 34,910 newbornchildren: resultsfroma13-year inci- Nielsen J, Wohlert M.Sex chromosome abnormalitiesfound Arq Bras Metab. Endocrinol 2012;56/8 ------Arq Bras Metab. Endocrinol 2012;56/8 21. 20. 19. 18. 7. 1 16. 15. 14. 13. 12. 11. 10. 9.

2011;336(1-2):198-205. tor-1 (SF-1, NR5A1)andhuman .MolCellEndocrinol. Ferraz-de-Souza B,LinL, Achermann JC.Steroidogenicfac- dysgenesis. Am JHumGen.1992;51:979-84. tions inXYfemaleswithcompleteratherthanpartial gonadal Berkovitz GD.EvidenceforincreasedprevalenceofSRY muta- Hawkins JR, Taylor A, GoodfellowPN,MigeonCJ, SmithKD, cases. Fertil Steril.2011;96(6):1431-14. accountsformorethanonethirdof tice: the46,XYkaryotype Maciel-Guerra AT. Completegonadaldysgenesisinclinicalprac- Rocha VB, Guerra-Júnior G,Marques-de-Faria AP, deMelloMP, 2009;70(2):173-87. ofsexdevelopment(DSD).ClinEndocrinol(Oxf). disorders Mendonca BB,DomeniceS, Arnhold IJ, CostaEM.46,XY 2003;32(2):198-200. palate: anewdiagnosticapproach. IntJOralMaxillofacSurg. nuclei ofbuccalmucosapatientsascertained byisolatedcleft ler R,PtokM,etal.Search fordeletion22q11.2 ininterphase Shouman N,Pabst B, Arslan-Kirchner M,Eckardt A, Schönwei- some. EurJPediatr. 2011;170(10):1325-7. tier G,Cornette L. andpentasomy oftheXchromo- Schoubben E,Decaestecker K,QuaegebeurDanneelsL,Mor covery. Fertil Steril.2001;75:1102-5. forsuccessfulspermre- factors studyofpossiblepredictive tive analysis inmenwithnonmosaicKlinefeltersyndrome:aprospec- Bergh C. Testicular ultrasonography andextendedchromosome Westlander E,GranbergS,HansonL,C, G,Ekerhovd 2011;26(12):3486-93. counselling.HumReprod.implications forgeneticreproductive F. HiddenmosaicisminpatientswithKlinefelter’s syndrome: Garcia-Quevedo L,BlancoJ, Sarrate Z,Català V, BassasL, Vidal A. 2005;138(3):259-61. mosaicism in Ullrich-Turner syndrome patients. Am J Med Genet Wiktor AE, Van DL.Detectionoflow level sexchromosome Dyke tients. JEndocrinolInvest. 2010;33(4):222-7. Y-chromosome in markers Turner syndrome:Screening of130 pa- Sallai A, Sólyom J, DobosM,SzabóJ, HalászZ,Ságodi L,etal. 2011;31(4):525-42. Tsuchiya KD.Fluorescenceinsituhybridization. ClinLabMed. the developmentofclinicalfeatures.HumGenet.1995;95:607-9 some aberrations: involved deductionoftheprincipalfactors in Ogata T, MatsuoN. Turner syndromeandfemalesexchromo- syndrome. Arq BrasEndocrinolMetab.2009;53(9):1137-42. mosome analysishasimproved thecytogeneticprofile of Turner Viguetti-Campos N,etal. The inclusionofnewtechniques ofchro- Barros BA,Maciel-Guerra AT, DeMelloMP, CoeliFB,Carvalho AB, ­ 35. 34. 33. 32. 31. 30. 29. 28. 27. 26. 25. 24. 23. 22. sis. Am JMedGenet.1996;66(2):187-92. with X and Y chromosome specific probes to buccal smear analy wald GW, etal. Application offluorescentinsitu hybridization Schad CR,Kuffel DG, Wyatt WA, Zinsmeister AR, Jenkins RB,De- Genet. 1991;88:49-52. a follow-up studyof39unselectedchildren foundatbirth. Hum Gravholt CH,Friedrich U, NielsenJ. Chromosomalmosaicism: Steril. 1985;43:229-33. the 46,XXcelllineina45,X/46,XX Turner mosaicpatient.Fertil McCorquodal MM,BowdleFC. Two pregnanciesandthelossof on use. Am JHumGenet.1977;29:94-7. cent, 95percentand99confidencelimi­ Hook EB.Exclusionofchromosome mosaicism:tablesof90per psychological features. Am JMedGenet A. 2008;146(12):1509-22. Reynolds A, etal. A newlook atXXYYsyndrome:medicaland Tartaglia N,DavisS,Hench S,BeauregardA, Nimishakavi R, 47,XYY aregistrystudy. persons: OrphanetJRare Dis.2010;5:15. Stochholm K,Juul S,Gravholt CH.Diagnosisandmortality in drome. JMedGenet.1969;6:159-65. XXYY mosaicismalsoshowingfeaturesofKlinefelter’s syn- Spencer DA, EylesJW, MasonMK.XYYsyndrome,andXYY/ Genet. 1999;56(1):59-65. of tissue-specificmosaicismin Turner syndromepatients.Clin Nazarenko SA, Timoshevsky VA, Sukhanova NN.Highfrequency diagnosed cases. Am JMedGenet.1994;53:108-40. euploidy withemphasisonstructuralaberrations inpostnatally Hsu LY. correlations Phenotype/karyotype of Y chromosome an- ranged Y chromosomes. HumReprod. 2006;21(4):972-5. cytogenetic studiesinthreeinfertile patientswithmosaicrear Bettio D, Venci A, RizziN,NegriL,Setti PL.Clinicalandmolecular 2012;97(8):E1540-9. – longitudinalstudy.A retrospective JClinEndocrinolMetab. phenotypic characteristics, function growth,andreproductive NE,etal.45,X/46,XYmosaicism: S, Petersen BL,Skakkebæk Lindhardt Johansen M,HagenCP, Rajpert-De MeytsE,Kjærgaard drome StudyGroup.JClinEndocrinolMetab.2007;92:10-25. women with Turner syndrome: a guideline of the Turner Syn- Bondy CA. Turner Syndrome StudyGroup.Careofgirlsand EndocrRev.tions, moving frontiers. 2006;27(5):468-84. gonad:oldpaths,newdirec- intheintersex Germ celltumors Cools M,DropSL, Wolffenbuttel KP, OosterhuisJW, Looijenga LH. 2010;51:223-4. gous mutationintheNR5A1gene:acasestudy. J Appl Genet. MP. CompleteXYgonadaldysgenesisduetop.D293Nhomozy Soardi FC,CoeliFB,Maciel-Guerra AT, Guerra-Junior G,Mello Molecular cytogenetics andhiddenmosaicism ts andcomments 551 - - - -

Copyright© ABE&M todos os direitos reservados.