AB= Aberdeen DUN = Dundee ED = Edinburgh GLA = Glasgow. Disease AB DUN ED GLA Service

Transcription

1 A current profile of disease and location for testing is provided below. Service: Molecular Genetics Service Summary: Tests by site A current profile of disease and location for testing is provided below. Key: AB= Aberdeen DUN = Dundee ED = Edinburgh GLA = Glasgow Disease Achondroplasia and other skeletal dysplasias Common mutations Acral peeling skin syndrome Sequence analysis of TGM5 Alpha 1 antitrypsin deficiency Z mutation only Alport syndrome COL4A3, COL4A4, COL4A5 NGS sequencing and COL4A5 Aneuploidy screening by QF PCR (prenatal and postnatal) Aneuploidy screening by QF PCR (pregnancy loss) QF-PCR for chromosome. 13,18,21, & Y QF-PCR for chromosome. 13,15, 16, 18,21, 22 & Y Angelman syndrome and UBE3A sequencing Arrhythmogenic right ventricular cardiomyopathy (ARVC) Autosomal recessive congenital ichthyosis (ARCI) Autosomal dominant polycystic kidney disease (ADPKD) Autosomal recessive polycystic kidney disease (ARPKD) PKP2 mutations, DSG2, DSP and DSC2 Sequence analysis of TGM1 ; ALO12B, NIPAL4 and CYP4F22. Sequence analysis of PKD1 and PKD2; Sequence analysis of PKHD1; Bardet Beidl syndrome Variant confirmation Beckwith Wiedemann MS- Biotinidase deficiency Sequence analysis of BTD Birt-Hogg-Dube syndrome FLCN sequencing and Breast/Ovarian Cancer BRCA 1 & 2 sequence/ ; RAD51C&D sequence Page 1 of 7

2 Bullous congenital ichthyosiform erythroderma (BCIE) Sequence analysis of KRT1 and KRT10 s Cadasil NOTCH3 sequencing Capillary malformations Sequence analysis of RASA1 ; Cerebral cavernous malformations (CCM) Sequence three CCM s; CHARGE syndrome CHD7 mutations and Choroideremia Linkage only Clove syndrome Common PIK3CA mutations Cowden Syndrome PTEN sequence/ Congenital hypothyroidism TG, TPO, TSHR sequencing and CPVT RYR2 sequence Crigler-Najjar syndrome Sequence analysis of UGT1A1 Cystic fibrosis (CF) Common mutations Deafness (GJB2, GJB6) Sequence analysis of GJB2 including c.-23+1g>a mutation; testing for GJB6 deletions Dentatorubral-pallidolusian atrophy (DRPLA) Developmental delay Common microdeletions: karrotype and array Di George syndrome (22q11 del) Dilated cardiomyopathy (DCM) 16 panel (see HCM entry) and separate Titin (cardiac isoform) testing by NGS Distal hereditary motor neuropathy Disorders of sexual development (DSD) HSPB1, HSPB3, HSPB8, GARS, BSCL2, TRPV4 sequence AR, SRY, MAMLD1, NR5A1, NR0B1, SRD5A2, HSD17B3 sequencing and Duchenne/ Becker muscular dystrophy (DMD/ BMD) DMD and sequencing Dystonia - torsion Testing for DYT1 deletion. Epidermolysis bullosa simplex (EBS) Epidermolytic palmoplantar keratoderma (EPPK) Sequence analysis of KRT5 and KRT14 Sequence analysis of KRT1 and KRT9 Fabrys disease Sequence analysis of GLA Page 2 of 7

3 Epileptic encephalopathy, early infantile STBP1 sequencing and Factor V Leiden Specific mutation Familial adenomatous polyposis (FAP) Sequence APC and MYH; for deletions Familial hypercholesterolaemia LDLR sequence/ & specific mutations in ApoB/PCSK9 Familial Mediterranean fever Exon 2 & Exon 10 MEFV Female-restricted epilepsy and mental retardation (EFMR) Fibrodysplasia Ossificans Progressiva (FOP) Fragile Mutation test Friedreichs ataxia Mutation test PCHD19 sequencing and ACVR1 P.R206H mutation Gilbert syndrome Common variant in UGT1 promoter Glomulovenous malformations Selected exons of glomulin; common mutations in TIE2 Glut1 deficiency Sequencing and GRA (hyperaldosteronism) Chimaeric fragments Haemochromatosis C282Y and H63D mutations Haemophilia B, Haemophilia A (sickle cell, Beta Thalassaemia, Alpha Thalassaemia) Hereditary neuropathy with liability to pressure palsy (HNPP) Hereditary Hemorrhagic Telangiectasia (HHT) and Primary Pulmonary Hypertension Hereditary motor & sensory neuropathy (HMSN, CMT) Hereditary sensory & autonomic neuropathy HBB sequencing, HBB, HBA PMP22 sequence/ ENG, ACVRL1, SMAD4, GDF2 (BMP9), BMPR2, SMAD9, CAV1, KCNK3 NGS ENG, ACVRL1, BMPR2 PMP22, P0,PMP22,C32, MFN2,LITAF, NEFL, EGR2, DNM2,GDAP1, DNM2, AARS, YARS, HSPB1, HSPB3, HSPB8, GARS, BSCL2, TRPV4, RAB7A, PDK3, PRPS1 sequence SPTLC1 sequence Page 3 of 7

4 Hereditary non-polyposis colorectal cancer (Lynch syndrome) Sequence analysis of MLH1, MSH2 and MSH6 s; Hereditary Spastic Paraplegia SPAST, ATL1 sequencing and Hirschsprung s disease (HSCR) Sequence analysis of RET HNPCC (microsatellite instability testing - MSI) Hypertrophic cardiomyopathy (HCM) Huntington disease Mutation test Microsatellite testing on tumour DNA to detect MSI; testing for common BRAF mutation 16 panel by NGS sequencing including MYBPC3, MYH7, TNNI3, TNNT2 and TPM1. Hypochondroplasia Common mutations Hypokalemic periodic paralysis 1 (HOKPP1) / hyperkalemic periodic paralysis (HYPP) Common mutations in CACN1AS and SCN4A s Ichthyosis bullosa of Siemens Sequence analysis of KRT2 Ichthyosis vulgaris Common FLG mutations Incontinentia pigmenti Common del. & inactivation Juvenile Polyposis syndrome BMPR1A, SMAD4 sequencing and Leber hereditary optic neuropathy (LHON) Common mutations Lesch-Nyhan syndome HPRT mutations Li Fraumeni TP53 sequence/ Lipoprotein lipase deficiency LPL sequence/; APOC2, APOA5, GPI-HBP1, LMF1 sequence Limb Girdle Muscular Dystrophy FKRP and LMNA sequencing and Loeys-Dietz syndrome Sequence analysis TGFBR1, TGFBR2; Long QT syndrome KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 (and KNCJ2 upon request) Marfan syndrome Sequence analysis of FBN1, TGFBR1 and TGFBR2; MCADD Sequence analysis of ACADM Disease Page 4 of 7

5 Hereditary Malignant Melanoma CDK2NA, CDK4 sequencing Mitochondrial disorders (not LHON) Methyl malonic aciduria (cobalamin deficiency) Sequence analysis for common point mutations. Exons 1-4 MMACHC MODY Sequence analysis of HNF1A, HNF4A, HNF1B and GCK; Multiple endocrine neoplasia type 1 Multiple endocrine neoplasia type 2a/2b and FMTC Sequence analysis of MEN1 Sequence analysis of RET MYH-associated polyposis Common MYH mutations; sequence analysis of MYH Myotonic dystrophy type 1 Mutation test Myotonic dystrophy type 2 Mutation test Nephronophthisis (familial juvenile) Common deletion NPH1 Neurofibromatosis (NF1) Sequence analysis of NF1; Oculopharyngeal muscular dystrophy (OPMD) Ornithine transcarbamylase deficiency (OTC) Screen for OPMD expansion; sequence analysis of 25 codons OTC screen Pachyonychia congenita Testing for mutations in conserved regions of KRT6.16 & 17 Parkinson s disease (early onset) Paroxysmal Kinesigenic Dyskenia Sequence analysis of PARK2 ; screen for common LRRK2 and PINK1 mutations; PRRT2 sequencing Page 5 of 7

6 Pelizaeus Merzbacher Sequence analysis of PLP1 and GJA12: for PLP1 Pendred syndrome-deafness Sequence analysis of SLC26A4 and FOI1 s; for SLC26A4 Peutz Jegher syndrome STK11 sequencing and Preimplantation Genetic Diagnosis (PGD) by preimplantation tic haplotyping (PGH) Phaeochromocytoma/ paraganglioma HFEA licensed conditions offered. If no license is listed referring centre should obtain one before referring family. Sequence analysis of SDHB/SDHC/SDHD, TMEM127 and MA s;. Phenylketonuria (PKU) PAH sequencing and Pontocerebellar hypoplasia 1/2 Sequence EOSC3 and TSEN54 for common mutations Prader Willi syndrome MS- Prothrombin (factor II) g.20210g->a mutation Proximal symphalangism Sequence NOG1; GDF5 RASMAPK testing (including Noonan syndrome, CFC, Leopard syndrome) 13 s within RASMAPK pathway by NGS Rett syndrome MECP2 mutations Russell-Silver syndrome (UPD7) Severe Myoclonic Epilepsy of Infancy (SMEI) Short Stature Homeobox (SHO) MS- and linked markers SCN1A mutations Sequencing and Sickle cell disease HBB Glu7Val sequence only Smith Lemil Opitz DHCR7 sequencing Spinal bulbular muscular strophy (SBMA, Kennedy s) Mutation test Spinal muscular atrophy (SMA) Common mutations, linkage Spinocerebellar ataxia (SCA) SCA1,2,3,6,7 & 8 mutations Stargardt disease Testing ABCA4 by NGS Thrombophilia Testing for p.arg506gln and g.20210g>a mutations Thoracic aortic aneurysms and dissections (TAAD) Additional testing for ACTA2 mutations Trimethylaminuria Exons 2-9 FMO3 Trisomy QFPCR Page 6 of 7

7 Tuberous sclerosis Sequence TSC1 and TSC2; for deletions Disease Type 3 hyperlipidaemia ApoE common variant screen Von Hippel-Lindau (VHL) Sequence VHL; White sponge naevus Sequence KRT4 and KRT13 -inactivation MS restriction digest -linked mental retardation Partial sequence PAK3, confirmation of familial mutations -linked ichthyosis STS sequencing and Y deletion Multiplex PCR to detect deletions; microsatellite markers Page 7 of 7