Disease

Gene/s

Technique

Alpha-1-antitrypsin

SERPINA1

Sanger sequencing

Alpha thalassaemia

HBA

MLPA [detects ~90% of pathogenic variants]

Alport syndrome

COL4A3, COL4A4, COL4A5

NGS (Ion Torrent PGM) with over 95% coverage at 20X

Congenital contractural arachnodactyly (CCA) or Beal’s syndrome

FBN2 (NM-001999.3) exons 17,18, 23-36

Sanger sequencing

Cornelia de Lange syndrome (CdLS) including atypical forms

NIPBL, SMC1A, SMC3, HDAC8, RAD21, ANKRD11, KMT2A & known pathogenic variants in AFF4 & NAA10 (p.Arg83Cys)

NGS (Ion Torrent PGM) with over 95% coverage at 20X.  Sanger sequence fill in and confirmations as required.

Craniodiaphyseal dysplasia (AD) / sclerostosis (AR)

SOST

Sanger sequencing

Craniofacial disorders

FGFR1 (NM_023110.2) exon 7,

FGFR2 (NM_000141.4) exons 8 & 10,

FGFR3 (NM_000142.4) exons 7 & 10,

TWIST1 (NM_00474.3) exon 1

Sanger sequencing

Cystic fibrosis and related conditions:

CFTR-related azoospermia

CFTR-related bronchiectasis

CFTR

CF-EU2, and/or Sanger sequencing, MLPA

Dilated cardiomyopathy (DCM)

ACTC1, CSRP3, LAMP2, MYBPC3, MYH7, MYL2 , MYL3, PLN , TNNC1, TNNI3, TNNT2, TPM1, TTN

NGS (Ion Torrent PGM) with over 95% coverage at 20X.  Sanger sequence fill in and confirmations as required.

DRPLA

ATN1

Fluorescent PCR amplification then fragment analysis

Early onset dementia / motor neuron disease

C9orf72

Flanking and triplet-primed fluorescent PCR amplification then fragment analysis

Early onset dementia / motor neuron disease

APP, CHMP2B, FUS, GRN, LRRK2, MAPT, PARK2, PSEN1, PSEN2, SOD1, SQSTM1, TARDBP, UBQLN2, VAPB, VCP

NGS (Ion Torrent PGM) with over 95% coverage at 20X.  Sanger sequence fill in and confirmations as required.

Fabry’s disease

GLA

Sanger sequencing and MLPA analysis

Familial amyloid polyneuropathy

TTR

Sanger sequencing

Familial hypocalciuric hypercalcaemia (FHH)

CASR

Sanger sequencing

FGFR3-related skeletal dysplasia:

Achondroplasia

Camptodactyly, tall stature and scoliosis and hearing loss (CATSHL) syndrome

Crouzon syndrome with acanthosis nigricans

Hypochondroplasia

Lacrimoauriculodentodigital (LADD) syndrome

Muenke syndrome

Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN)

Thanatophoric dysplasia types I and II

FGFR3 (NM_000142.4) exon 7, 10, 13, 15, 19

Sanger sequencing of exon(s) containing common variant(s)

Fragile-X syndrome and related conditions:

Fragile X tremor ataxia syndrome

Premature ovarian failure / insufficiency

FMR1

Flanking and triplet-primed fluorescent PCR amplification then fragment analysis

Friedreich’s ataxia

FXN

Fluorescent PCR amplification then fragment analysis and Sanger sequencing for point mutation analysis

Haemoglobinopathies and beta thalassaemia

HBB

Sanger sequencing and MLPA analysis

Hereditary haemorrhagic telangiectasia (HHT)

ACVRL1, ENG, GDF2, SMAD4

NGS (Ion Torrent PGM) with over 95% coverage at 20X.  Sanger sequence fill in and confirmations as required and MLPA analysis.

Huntington disease (HD)

HTT

Fluorescent PCR amplification of repeat for diagnostic and predictive referrals. Exclusion work-ups by linked markers.

Hypertrophic cardiomyopathy (HCM)

ACTC1, CSRP3, FHL1, GLA, LAMP2, MYBPC3, MYH7, MYL2, MYL3, PLN , PRKAG2, TNNC1, TNNI3, TNNT2, TPM1, TTR

NGS (Ion Torrent PGM) with over 95% coverage at 20X.  Sanger sequence fill in and confirmations as required.

Infantile myofibromatosis Type 1

PDGFRB common variants c.1681C>T, p.(Arg561Cys) & c.1978C>A, p.(Pro660Thr)

Sanger sequencing

Infantile myofibromatosis Type 2

NOTCH3 c.4556T>C, p.(Leu1519Pro)

Sanger sequencing

Juvenile polyposis syndrome (JPS) and JPS/HHT

BMPR1A & SMAD4

Sanger sequencing and MLPA analysis

Late onset retinal macular degeneration

C1QTNF5 (CTRP5) c.489C>G or c.489C>A  p.(Ser163Arg)

Sanger sequencing

Lynch syndrome / Hereditary non polyposis colorectal cancer (HNPCC)

MLH1, MSH2, MSH6, MUTYH (NM_001128425.1) exons 7 & 13, PMS2

MSH2, MSH6, PMS2- Sanger sequencing and MLPA analysis.

N.B. PMS2 only when isolated loss of PMS2 has been detected by IHC or when Turcot syndrome is suspected.

Lynch syndrome / Hereditary non polyposis colorectal cancer (HNPCC)

n/a

Microsatellite instability testing of tumour DNA (Promega MSI analysis system v1.2)

Microcephaly 5, primary, autosomal recessive (MCPH5)

ASPM

Sanger sequencing and MLPA analysis

Microcephalic osteodysplastic primordial dwarfism, type II (MOPD II).

PCNT

Sanger sequencing

Myotonic dystrophy (DM1)

DM1

Flanking and triplet-primed fluorescent PCR amplification then fragment analysis

Nocturnal frontal lobe epilepsy (AD)

CHRNA4 (NM_000744.6) exon 5 & CHRNB2 (NM_000748.2) exon 5

Sanger sequencing

Ocular malformations

 

ACTB, ACTG1, ALDH1A3,  BCOR,  C12ORF57, CHD7, COL4A1, FOXC1, FOXE3, FZD5, GJA8, ITPA, ITPR1, MAB21L1, MAB21L2,  NAA10, OTX2, PAX2, PAX6, PITX2, PITX3, RAB18, RAB3GAP1, RAB3GAP2, RARB, RAX, RBP4, SALL2, SALL4, SHH, SIX3, SMCHD1, SMOC1, SOX2, STRA6, TBC1D20, VAX1, VSX2, YAP1, ZEB2, ZIC2.

NGS (Illumina MiSeq) with over 95% coverage at 20X.  Sanger sequence confirmations as required.

Ornithine transcarbamylase deficiency (OTC)

OTC

Sanger sequencing and MLPA analysis

Pagets disease of bone

SQSTM1 (NM_003900.4)exons 7 & 8.

Sanger sequencing

Peutz Jegher syndrome

STK11

Sanger sequencing and MLPA analysis

PGD

Please enquire

 Pre-implantation Genetic Haplotyping (PGH)

Polymerase proofreading-associated polyposis (PPAP).  

POLD1 (NM_000748.2)exon 12 & POLE (NM_006231.2) exon 13

Sanger sequencing

Primary pulmonary hypertension

BMPR2, CAV1, KCNK3 and SMAD9

NGS (Ion Torrent PGM) with over 95% coverage at 20X.  Sanger sequence confirmations as required.

Primordial dwarfism and microcephaly disorders

ASPM, ATR, ATRIP, BLM, CASC5, CASK, CDC45, CDC6, CDK5RAP2, CDT1, CENPE, CENPF, CENPJ, CEP135, CEP152, CEP63, CREBBP, DNA2, DPP6, DYRK1A, EP300, GMNN, IGF1, IGF1R, KIF11, LARP7, LIG4, MCPH1, MRE11A, NBN, NDE1, ORC1, ORC4, ORC6, PCNT, PHC1, PLK4, POC1A, RAD50, RBBP8, RNU4ATAC, SRCAP, STIL, TCF4, TRAIP, TUBGCP6, VPS13B, WDR4, WDR62, XRCC4.

NGS (Illumina MiSeq) with over 95% coverage at 20X.  Sanger sequence confirmations as required.

Prion disease and related conditions:

 Creutzfeldt-Jakob disease (CJD)

 Gerstmann-Straussler disease

Huntington disease-like 1

Fatal familial insomnia

PRNP

Sanger sequencing and octapeptide repeat sizing by flanking fluorescent PCR

RAS-MAPK related:

Noonan syndrome

Cardio-facio-cutaneous syndrome

Costello syndrome

 LEOPARD syndrome

 Neurofibromatosis type 1

 

RAS-MAPK pathway (BRAF, CBL, HRAS, KRAS, MAP2K1, MAP2K2, NF1, NRAS, PTPN11, RAF1, SHOC2, SOS1, SPRED1, RIT1)

NGS (Ion Torrent PGM) with over 95% coverage at 20X.  Sanger sequence fill in and confirmations as required

Retinal dystrophy:

Stargardt disease 1

Cone rod dystrophy 3

 Fundus flavimaculatus

Retinitis pigmentosa 19

ABCA4

NGS (Ion Torrent PGM) with 100% coverage of coding and flanking intronic region

Spinal muscular atrophy

SMN1

MLPA analysis

Spinocerebellar ataxia 8 (SCA8)

ATXN8 / ATXN8OS

Fluorescent PCR amplification then fragment analysis

Spinocerebellar ataxia 17 (SCA17)

TBP

Fluorescent PCR amplification then fragment analysis

Spinocerebellar ataxia screen (SCA 1,2,3,6,7)

ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7

Fluorescent PCR amplification then fragment analysis

X-linked spinal bulbar muscular atrophy (X-SBMA, Kennedy disease)

AR

Fluorescent PCR amplification then fragment analysis

 

Last Reviewed: 31/01/2017