Dermatology Gene Panel
Contact details Introduction Regional Genetics Service Inherited conditions affecting the skin are a diverse group of genetically heterogeneous Levels 4-6, Barclay House disorders. Inheritance may be autosomal dominant, recessive, or X-linked, and mosaic 37 Queen Square dermatological conditions are increasingly recognised. Where conditions are highly heterogeneous a panel of known causative genes are tested to maximise clinical sensitivity and London, WC1N 3BH minimise time to diagnosis. T +44 (0) 20 7762 6888 F +44 (0) 20 7813 8578 Referrals Patients presenting with symptoms consistent with the genes and conditions listed. Samples required Referrals will be accepted from clinical geneticists and consultants in dermatology and 5ml venous blood in plastic EDTA paediatrics bottles (>1ml from neonates) Prenatal testing Prenatal testing must be arranged in advance, through a Clinical Prenatal diagnosis may be offered as appropriate where pathogenic variants have been Genetics department if possible. identified in accordance with expected inheritance pattern and appropriate parental testing and Amniotic fluid or CV samples counselling has been conducted. should be sent to Cytogenetics for dissecting and culturing, with Service offered instructions to forward the sample Analysis of coding regions and intron/exon boundaries of the genes listed in the sub-panels. If to the Regional Molecular Genetics no clearly pathogenic variant is identified, re-analysis of the clinical exome data may be offered laboratory for analysis for other dermatology sub-panels or other loci as appropriate. A completed DNA request form should accompany all samples Dermatology virtual panels (see page 2 for gene lists): Mendelian disorders of cornification / palmoplantar keratodermas Patient details Ectodermal disorders To facilitate accurate testing and Connective/adipose tissue disorders reporting please provide patient RASopathies and pigmentary disorders demographic details (full name, date of birth, address and ethnic origin), details Cutaneous vascular disorders of any relevant family history and full Inflammatory skin disorders contact details for the referring clinician Progeroid/premature ageing syndromes DNA repair disorders Epidermolysis bullosa/skin fragility Technical
Variant screening is carried out by next generation sequencing (NGS) with library preparation using the Agilent focused clinical exome +1 kit followed by sequencing on the Illumina NextSeq. Data is analysed using an in-house pipeline with all likely or clearly pathogenic variants confirmed by Sanger sequencing. Target reporting time
4 months for a full NGS screen in an index case. 4 weeks for familial testing. Please contact the laboratory for urgent cases
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Dermatology Gene Panel
Dermatology virtual panels:
Mendelian disorders of cornification and palmoplantar keratodermas (CORN_v2): AAGAB, ABCA12, ABHD5, ADAM17, ALDH3A2, ALOX12B, ALOXE3, AP1S1, AQP5, ARSE, CDSN, CERS3, CLDN1, CSTA, CTSC, CYP4F22, DSC2, DSC3, DSG1, DSG4, DSP, EBP, ELOVL4, FLG, GJB2, JUP, KANK2, KRT1, KRT10, KRT2, KRT6C, KRT9, LIPN, LOR, MBTPS2, NIPAL4, PEX7, PHYH, PKP1, PNPLA1, RHBDF2, SASH1, SLC27A4, SLURP1, SNAP29, SPINK5, ST14, STS, TGM1, TRPV3, VPS33B Ectodermal disorders (ECTODERM_v2): ADAM10, ARSE, ATP2A2, ATP7A, ATR, CAST, CDH3, CDSN, DCLRE1C, DKC1, DSC2, DSC3, DSG1, DSG4, DSP, EDA, EDA2R, EDAR, EDARADD, GJA1, GJB2, GJB3, GJB4, GJB6, GRHL2, HOXC13, HR, IKBKG*, JUP, KANK2, KRT1, KRT14, KRT16, KRT17, KRT5, KRT6A, KRT6B, KRT85, LAMA3, LAMB3, LIPH, LPAR6, MBTPS2, MSX1, NFKBIA, PKP1, POFUT1, POGLUT1, PORCN, PVRL1, PVRL4, RAG1, RAG2, RECQL4, RIN2, SHOC2, SLC29A3, SMARCAD1, SOX18, TP63, TWIST2, USB1, WNT10A Connective/adipose tissue disorders (CAD_v2): ABCC6, ADAMTS2, ALDH18A1, ATP6V0A2, B3GALT6*, B4GALT7, BANF1, CECR1, CHST14, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, DSE, ECM1, EFEMP2, ELN, FBLN5, FBN1, FKBP14, LEMD3, LMNA, PLOD1, PRDM5, PYCR1, RIN2, SLC39A13, TGFBR1, TGFBR2, TNXB*, ZMPSTE24, ZNF469 RASopathies and Pigmentary disorders (PIGMENT_v3): ABCB6, ABCD4, ADAM10, ADAR, AP3B1, ARSE, BAP1, BRAF, CBL, CDK4, CDKN2A, DKC1, EDN3, EDNRB, ENPP1, FGF23, FLNA, GALNT3, GJA1, GJB3, GJB4, GNA11, GNAQ, GNAS, HPS1, HRAS, KIT, KITLG, KRAS, KRT14, KRT5, LYST, MAP2K1, MAP2K2, MC1R, MITF, MLH1, MSH2, MSH6, MTOR, MYO5A, NF1, NF2, NOP10, NRAS, OCA2, OSMR, PALB2, PAX3, PIK3CA, PMS2, POFUT1, POGLUT1, PORCN, PRKAR1A, PTEN, PTPN11, RAB27A, RAF1, RECQL4, RIT1, SAMD9, SASH1, SHOC2, SLC24A5, SLC29A3, SLC45A2, SLX4, SNAI2, SOS1, SOX10, SOX18, SPRED1, STK11, TERC, TERT, TINF2, TSC1, TSC2, TYR, TYRP1, USB1, WRAP53 Vascular disorders (VASCULAR_v2): ATM, ATR, CCBE1, ENG, F12, FLT4, FOXC2, GLMN, GNA11, GNAQ, KDR, KRIT1, PIK3CA, PIK3R2, RASA1, SCN9A, SMAD4, SOX18, TEK, TMEM173 Inflammatory skin disorders (ISD_v2): CARD14, CECR1, CSTA, CYBB, DCLRE1C, DOCK8, EDA, FLG, GJA1, GJB3, GJB4, IKBKG*, IL1RN, IL36RN, KIT, KRT1, KRT10, OSMR, RAG1, RAG2, SAMHD1, SLC39A4, STAT3, TMEM173, TREX1 Progeria/premature ageing (PROGERIA_v2): B3GALT6*, B4GALT7, BANF1, DKC1, ERCC2, ERCC4, ERCC5, ERCC6, LMNA, RECQL4 DNA repair disorders (DRD_v3): ALAS2, BLM, BRCA2, BRIP1, CDAN1, DDB2, ERCC2, ERCC3, ERCC4, ERCC5, ERCC6, ERCC8, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, GTF2H5, MLH1, MPLKIP, MSH2, MSH6, NOP10, PALB2, PMS2, POLH, RAD51C, SLX4, TERC, TERT, TINF2, WRAP53, XPA, XPC Epidermolysis bullosa/skin fragility (EBF_v2): CAST, CD151, CDSN, COL17A1, COL7A1, CSTA, DSC2, DSC3, DSG1, DSG4, DSP, DST, EXPH5, FERMT1, ITGA3, ITGA6, ITGB4, JUP, KRT14, KRT5, LAMA3, LAMB3, LAMC2, PKP1, PLEC, TGM5 *Genes marked with an asterisk have low (<90%) horizontal coverage due to sequence context and/or the presence of highly homologous regions in the genome.
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