Service: Molecular Genetics Service Summary: Tests by site AB ...

Service:Molecular GeneticsService Summary: Tests by siteA current profile of disease and location for testing is provided below.AB= Aberdeen DUN = Dundee ED = Edinburgh GLA = GlasgowDiseaseAB DUN ED GLA ServiceAchondroplasia X Common mutationsAcral peeling skin syndrome X Sequence analysis of TGM5 geneAneuploidy screening (pre &postnatal) by QF PCRAneuploidy screening(pathology) by QF PCRX X X X QF-PCR; chr. 13,18,21, X & YXQF-PCR; chr. 13,15,16,18,21,22, X& YAngelman syndrome X MS MLPA & UBE3A sequencingARVC X PKP2 mutations, DSG2 and DSPAutosomal dominantpolycystic kidney disease(ADPKD)Autosomal recessivepolycystic kidney disease(ARPKD)XXMicrosatellite analysisSequence analysis of PKHD1;deletion testing by MLPABardet-Biedl syndrome 1 X Common M390R mutationBeckwith-Wiedemann syn X MS MLPA, UPD chr 11Biotinidase deficiency X Sequence analysis of BTD geneBirt-Hogg-Dube X FLCN gene sequencingBreast Cancer X BRCA 1 & 2, P53, PTEN genesequencing & MLPA.RAD51C & D gene sequencingBullous congenitalichthyosiform erythroderma(BCIE)XSequence analysis of KRT1 andKRT10 genesCADASIL X NOTCH3 gene sequencingCerebral cavernousmalformations (CCM)XSequence CCM genes; deletiontesting by MLPACHARGE syndrome X CHD7 gene sequencing & MLPAChoroideremia X Linkage onlyCongenital Hypothyroidism X TSHR, TPO & TP gene sequencing1

DiseaseAB DUN ED GLA ServiceCPVT X RYR2 gene sequenceCrigler-Najjar syndrome X Sequence analysis of UGT1A1geneCystic fibrosis (CF) X X X X Common mutationsCystic fibrosis (CF) NewbornscreeningX5 mutation screenDeafness (GJB2, GJB6) X Sequence analysis of GJB2 geneincluding c.-23+1G>A mutation;testing for GJB6 deletionsDentatorubral-pallidolusianatrophy (DRPLA)Developmental delay X X X X Commonmicrodeletions/duplications &telomeresDi George syndrome (22q11del)XX X MicrodeletionsDilated cardiomyopathy X LMNA gene sequencingDuchenne/ Becker musculardystrophy (DMD/ BMD)XMLPA & Dystrophin genesequencingDystonia - torsion X X Testing for DYT1 deletion.Epidermolysis bullosasimplex (EBS)Epidermolytic palmoplantarkeratoderma (EPPK)XXSequence analysis of KRT5 andKRT14Sequence analysis of KRT1 andKRT9Factor V Leiden X X X Specific mutationFamilial adenomatouspolyposis (FAP)FamilialhypercholesterolaemiaFamilial juvenilenephronophthisisFibrodysplasia OssificansProgressiva (FOP)XXXXSequence APC and MYH; MLPA fordeletionsLDLR sequence & specificmutationsTest for homozygous deletionSpecific mutationFragile X X X X Mutation testFriedreichs ataxia X Mutation testGastrointestinal stromaltumours (GISTs)XSequence analysis of selectedexons of KIT and PDGFRA genes.Gilbert syndrome X Common mutation in UGT1promoterGRA (hyperaldosteronism)X2

DiseaseAB DUN ED GLA ServiceHaemochromatosis X X X Common mutationsHereditary liability topressure palsy (HLPP)Hereditary HemorrhagicTelangiectasia (HHT)Hereditary motor sensoryneuropathy (HMSN, CMT)Hereditary non-polyposiscolorectal cancer (HNPCC)Hereditary spasticparaplegiaHirschsprung’s disease(HSCR)HNPCC (microsatelliteinstability testing - MSI)XXXCommon mutationsENG, ALK1, SMAD4 mutationsMLPA, P0,PMP22,CX32 mutationsX X Sequence analysis of MLH1, MSH2and MSH6 genes; deletion testingby MLPAXXXSpastin & atlastin gene sequencingSequence analysis of RET geneMicrosatellite testing on tumourDNA to detect MSI; testing forcommon BRAF mutationHOCM X TNNT2,MYH7 mutationsHuntington disease X Mutation testHydatidiform molarpregnancyXMicrosatellite markersHypochondroplasia X Common mutationsHypokalemic periodicparalysis 1 (HOKPP1) /hyperkalemic periodicparalysis (HYPP)Ichthyosis bullosa ofSiemensXXCommon mutations in CACN1ASand SCN4A genesSequence analysis of KRT2 geneIchthyosis vulgaris X Common FLG mutationsIchthyosis; recessivecongenital formXSequence analysis of TGM1 andALOX12B genesInfantile onset epilepsy X SCN1A, PCDH19, SLC2A1, CDKL5& ARX gene sequencing & MLPA.STBXBP1 gene sequencing.Incontinentia pigmenti X NEMO gene common deletion & X-inactivationKallman syndorme X MLPA for KAL1 geneKRAS testing X Screen for common mutationsLeber hereditary opticneuropathy (LHON)XCommon mutationsLesch-Nyhan syndome X HPRT1 gene sequencing & MLPALimb girdle musculardystrophy type 2IXFKRP gene sequencing3

DiseaseAB DUN ED GLA ServiceLong QT syndrome X KCNQ1, KCNH2, SCN5A , KCNE1,KCNE2 and other gene sequencesMarfan syndrome X Sequence analysis of FBN1MCAD X Sequence analysis of ACADM geneMedullary thyroid carcinoma X Sequence analysis of selected RETexonsMelanoma X Sequence analysis of selected KITexonsMelanoma X CDKN2A & CDK4 gene sequencingMitochondrial disorders (notLHON)Methylenetetrahydrofolatereductase deficiency(MTHFR)Multiple endocrine neoplasiatype 1Multiple endocrine neoplasiatype 2a/2bXXXXSequence analysis for commonpoint mutations.C677T mutationSequence analysis of MEN1 geneSequence analysis of selected RETexonsMYH-associated polyposis X X Common MYH mutations;sequence analysis of MYH geneMyotonic dystrophy type 1 X X X X Mutation testMyotonic dystrophy type 2 X Mutation testNephronophthisis (familialjuvenile)XCommon deletion NPH1Neurofibromatosis (NF1) X Microsatellite markersNeurofibromatosis (NF1) X Deletion screen by MLPANeurohypophyseal diabetesinsipidusOculopharyngeal musculardystrophy (OPMD)Ornithine transcarbamylasedeficiency (OTC)XXXAVP gene sequencingScreen for OPMD expansion;sequence analysis of 25 codonsOTC gene screenOvarian Cancer X BRCA 1 & 2, P53, PTEN genesequencing & MLPA.RAD51C & D gene sequencingPachyonychia congenita X Confirm identified mutationParkinson’s disease (earlyonset)Peeling skin syndrome(PSS)XXSequence analysis of PARK2 gene;screen for common LRRK2mutation; deletion testing by MLPASequence analysis of TGM5 genePelizaeus Merzbacher X Sequence analysis of PLP1 gene;dosage analysis by MLPA4

DiseaseAB DUN ED GLA ServicePeutz Jeghers syndrome X Sequence STK11; MLPAPhaeochromocytoma/paragangliomaPhaeochromocytoma/paragangliomaXXSequence analysis ofSDHB/SDHC/SDHD genes.Sequence SDHB/SDHC/SDHD;MLPAPhenylketonuria X PAH gene sequencingPrader Willi syndrome X MS MLPAProthrombin (factor II) X X X g.20210G->A mutationProximal symphalangism X Sequence NOG1; GDF5Retinoblastoma X RB1 mutations; MLPARett syndrome X MECP2 gene sequencing & MLPARussell-Silver syndrome(UPD7)Severe Myoclonic Epilepsyof Infancy (SMEI)XXLinkageSCN1A mutationsShort stature X MLPA & sequencing of SHOXgeneSickle cell disease X X HBB Glu7Val mutationSickle cell disease (Newbornscreening)XHBB Glu7Val mutationSilver-Russell syndrome X MS MLPA for 11p15 & UPD chr 7Smith-Lemli-Opitz syndrome X DHCR7 gene sequencing & assayfor common mutationSpinal bulbular muscularstrophy (SBMA, Kennedy’s)Spinal muscular atrophy(SMA)Spinocerebellar ataxia(SCA)XXXMutation testCommon mutations, linkageSCA1,2,3,6,7 & 8 mutationsThrombophilia X X X Testing for p.Arg506Gln andg.20210G>A mutationsVon Hippel-Lindau (VHL) X Sequence VHL; MLPAX-inactivationX-linked ichthyosis X MLPA for STS gene deletion &sequencingX-linked mental retardation X Linkage, some mutation testingY deletion X X Screening of AZF regions a,b & cX5