Laboratory User Guides

Transcription

1 CLINICAL GENETIC SERVICE Laboratory User Guides (Website version) January 2016 DEPARTMENT OF HEALTH GOVERNMENT OF HONG KONG SAR Page 1 of 10

2 Compared with the previous version of January 2015, several new items are implemented: 1. Common cancer NGS panel. 2. Polycystic kidney diseases NGS panel. 3. SOX2 gene testing. 4. ANTXR2 gene testing. Last updated on 12 January 2016 Page 2 of 10

3 The Clinical Genetic Service of the Department of Health in Hong Kong is a government-funded, tertiary referral centre that provides clinical, laboratory, counseling services related to genetic disorders. The function of the Genetic Laboratory is to back up Genetic Counseling Clinic within this Service. Presently the Laboratory accepts specimens only via the Genetic Counseling Clinic of the Clinical Genetic Service. For more information about the laboratory service, please call Enquire Telephone : (852) Fax : (852) so_cg@dh.gov.hk 1. Clinical Specimens Specimen Submission Information Cytogenetic testing: Molecular testing: 3 ml heparin blood 1 to 2 ml more for additional FISH study 3 ml EDTA blood Samples need to be identified accurately and patient should not be fasted for overnight. The container of specimen shall be labeled with patient s name (in capital letters) and the HK/Travel document number (2 unique identifiers). Each specimen must be accompanied with a requisition form. Please fill patient name in capital letters and the HK/Travel document number on the requisition form, which SHALL also include the followings: - Date of birth and sex - Date of specimen taken Remarks: - Date of request Blood will be rejected if clotted, hemolyzed or - Type of specimen quantity insufficient for Cytogenetic testing - Name and signature of physician requesting test - Name and institution of referring doctor - Type of test requested - Pedigree (if needed) 2. Delivering Specimens After blood taken, specimen should be delivered at the same day (before 5 PM) as soon as possible - Deliver at room temperature; - Store at 4 o C if unable to deliver at the same day. Never ice or freeze the blood; - In a plastic bag separately with the Requisition Form. To: 2/F, Laboratory, Cheung Sha Wan Jockey Club Clinic 2 Kwong Lee Road, Sham Shui Po Kowloon, Hong Kong Tel: (attention: Ms. Tse) (NEW) For operational need, it is advised to take blood and send on Monday or Tuesday or Friday for Cytogenetic testing. For DEB fragility testing, it is advised to take blood and send on Monday or Tuesday with the control sample. Whenever possible, the control should be appropriately matched with the characteristics of the test sample, such as sex, age, cigarette smoking and undercurrent illness. Further re-arrangement is necessary for the blood taken and delivery during or before public holidays. 3. Turnaround Time () For routine service cases: Cytogenetic testing: 28 calendar days (shortened) FISH: Molecular testing: 2- (refer to the table below) (shortened) For urgent cases: Cytogenetic testing: 8 calendar days Molecular testing: 7 calendar days for prenatal testing (mutation(s) must has been identified) and MLPA for trisomy 14 calendar days for mutational screening testing (amplicons < 10) Page 3 of 10

4 14 calendar days for an additional Southern blot based testing Cytogenetics Service Conventional Cytogenetic s for Blood G banding DEB fragility study C staining Molecular Cytogenetics (FISH) s Telomere probes Whole chromosome painting probes Microdeletion probes Cri du Chat syndrome DiGeorge syndrome Kallman syndrome Miller Dieker syndrome Prader Willi / Angelman syndrome Retinoblatoma (Rb) Smith Magenis syndrome Steroid sulphatase deficiency Williams syndrome Wolf-Hirschhorn syndrome SRY Locus 5p q11.2 Xp p q q14 17p11.2 Xp22.3 7q p16.3 Yp11.3 Page 4 of 10

5 Molecular Service Next Generation Sequencing and MLPA Targeted Panels (NEW) Common cancer panel NEW - BRCA1, BRCA2, PTEN, TP53, MLH1,MSH2, MSH6, PMS2, EPCAM, APC, MUTYH deletion / duplication DMD panel - DMD deletion / duplication Marfan and aortopathy panel - FBN1, TGFBR1, TGFBR2, SMAD3, deletion / duplication SLC2A10, MYLK, MYH11, COL3A1, ACTA2 NF panel Polycystic kidney diseases panel NEW - NF1, NF2 deletion / duplication - PDK1, PKD2, PKHD1, HNF1B deletion / duplication CHROMOSOMAL ABNORMALITIES Intellectual Disability () related microdeletion syndromes - 11 loci causing syndromes deletion Subtelomeric deletion/duplication - Telomeres deletion / duplication Trisomies - chromosomes 13, 18, 21 trisomy 13, 18, 21 CRANIOSYNOSTOTIC SYNDROME Antley-Bixler syndrome POR Apert syndrome Crouzon Syndrome Pfeiffer syndrome FGFR2 Saethre-Chotzen syndrome TWIST deletion EYE DISEASES Aniridia PAX6 / deletion Cone-Rod dystrophy, type CRX Corneal dystrophy, lattice type TGFBI Congenital fibrosis of the extraocular muscles, type KIF21A Norrie disease NDP Peters plus syndrome B3GALTL Page 5 of 10

6 SOX2-related eye disorder SOX2 NEW HEARING LOSS Branchio-oto-renal syndrome, type EYA1 Deletion / duplication Deafness, congenital, with inner ear agenesis, microtia, and microdontia FGF3 Non-syndromic deafness GJB2 / GJB6 / deletion Mito - RNR1 m.1555a>g Waardenburg syndrome, type PAX3 / deletion HEART DISEASE Non-syndromic congenital heart disease NKX2-5 HEMATOLOGY -Thalassemia -globin region Southeast Asia type deletion / rightward or leftward deletion Hemophilia A F8 Introns 1 & 22 inversion linkage analysis* Hemophilia B F9 / deletion INBORN ERRORS of METABOLISM Fabry disease GLA Hypothyroidism, athyroidal, with spiky hair and cleft palate Hypothyroidism, choreoathetosis, neonatal respiratory distress FOXE1 / deletion NKX2-1 / deletion Hypothyroidism, congenital, nongoitrous, type TSHR / deletion Hypothyroidism, congenital, nongoitrous, type 2 Infantile systemic hyalinosis Leigh syndrome PAX8 / deletion ANTXR2 NEW SURF1 Mitochondrial disorder panel MELAS (m.3243a>g) MERRF (m.8344a>g) NARP (m.8993t>g) LHON (m.3460g>a, m.11778g>a, m.14484t>c) Mitochondrion Point mutation Mowat-Wilson syndrome ZEB2 / deletion Page 6 of 10

7 Mucolipidosis II / Mucolipidosis III / GNPTAB Mucopolysaccharidosis type II S Pyruvate dehydrogenase E1- deficiency PDHA1 / deletion Wilson disease ATP7B / deletion MALIGNANCY Multiple endocrine neoplasia type 2A Multiple endocrine neoplasia type 2B Familial medullary thyroid carcinoma RET / deletion Peutz-Jeghers syndrome STK11 Retinoblastoma RB1 / deletion Schwannoma, vestibular nerve tumor SMARCB1 / deletion Von Hippel-Lindau syndrome VHL / deletion NEUROLOGY Amyotrophic lateral sclerosis SOD1 Charcot-Marrie-Tooth disease, 1A PMP22 Gene duplication Hereditary Neuropathy with liability pressure palsies PMP22 Gene deletion Charcot-Marrie-Tooth disease, 1B MPZ Charcot-Marrie-Tooth disease, X-linked, GJB1 Congenital central hypoventilation syndrome PHOX2B / polyalanine expansion Dystonia, AD DYT1 GAG deletion Fragile X syndrome FMR1 CGG expansion Fragile X syndrome, type E AFF2 GCC expansion Friedreich ataxia FXN GAA expansion Huntington disease HTT Pelizaeus-Merzbacher disease Spastic paraplegia 2, X-linked PLP gene duplication Spastic paraplegia 44, AR GJC2 Spinocerebellar ataxias panel: SCA1 SCA2 SCA3 SCA ATXN ATXN ATXN CACNA1A Page 7 of 10

8 SCA7 SCA8 SCA12 SCA17 Dentatorubral-pallidoluysian atrophy ATXN7 ATXN80S PPP2R2B TBP ATN1 CTG expansion Subcortical band heterotopias, X-linked DCX / deletion NEURO-MUSCULAR DISEASES Duchenne muscular dystrophy DMD Exon(s) deletion / duplication linkage analysis** Kennedy s disease AR Myotonic dystrophy, type 1 (PCR) Myotonic dystrophy (Southern blot) DMPK CTG expansion 3 months Myotonic dystrophy, type CNBP CCTG expansion Oculopharyngeal muscular dystrophy PABPN1 GCG insertion Spinal muscular atrophy SMN1 Exons 7&8 deletion RENAL DISEASES Alport syndrome, AD COL4A5 linkage analysis** Alport syndrome, AR COL4A3 Nephrogenic diabetes insipidus AVPR2 / deletion Polycystic kidney disease, AD PKD1 & PKD2 / deletion linkage analysis** Polycystic kidney disease, AR ARPKD linkage analysis** DERMATOLOGIC DISORDER Ectodermal dysplasia 1, hypohidrotic, X-linked EDA / deletion Epidermolysis bullosa dystrophica, AR COL7A1 Incontinentia pigmenti NEMO exons 6-12 deletion SKELETAL DYSPLASIA Achondrogenesis, type Ib Diatrophic dysplasia Epiphyseal dysplasia, multiple, SLC26A2 Achondroplasia FGFR3 c.1138g>a Atelosteogenesis type 1 and type FLNB Page 8 of 10

9 Larsen syndrome Brachydactyly type B ROR2 Campomelic dysplasia SOX9 Chondrodysplasia with joint dislocations, GRAPP type Cleidocranial dysplasia Desbuquois dysplasia Fibrodysplasia Ossificans Progressiva Hypochondroplasia IMPAD1 Point mutation RUNX2 / deletion CANT ACVR FGFR3 c.1620c>g or C>A Hypophosphatatemic rickets, AD FGF23 Hypophosphatatemic rickets, X-linked PHEX Leri-Weill dyschondrosteosis Langer mesomelic dysplasia SHOX gene deletion Metaphyseal chondrodysplasia, McKusick type RMRP Multiple exotoses EXT1 / deletion Nail-patella syndrome LMX1B / deletion Pseudoachondroplasia COMP GAC expansion Pseudohypoparathyroidism GNAS copy number & methylation TP63-related disorder - TP63 Thanatophoric Dysplasia I FGFR3 Schwartz-Jampel syndrome type LIFR SEX DISORDER 46XY Sex reversal 46XX Sex reversal SRY The presence of SRY SYNDROMES / DYSMORPHOLOGY Angelman syndrome UBE3A Beckwith-Wiedemann syndrome Russell-Silver syndrome Blepharophimosis-Ptosis-Epicanhus- Inversus syndrome (BPES) H19DMR & copy number & KvDMR domains methylation CDKN1C FOXL2 / deletion Costello syndrome HRAS Page 9 of 10

10 Craniofrontonasal syndrome EFNB1 / deletion Spondylocostal dysostosis 2, AR MESP2 Spondyloepiphyseal dysplasia with congenital joint dislocation CHST3 Li-Fraumeni syndrome TP53 / deletion LOWE syndrome Noonan syndrome OCRL PTPN11 Prader Willi syndrome (PWS) / Angelman syndrome (AS) PWS / AS critical region at 15q11- q13 Microdeletion / Uniparental disomy at 15q11-q13 Rett syndrome MECP2 / deletion Simpson-Golabi-Behmel syndrome, type GPC3 / deletion Sotos syndrome NSD1 / deletion Van der Woude syndrome Popliteal pterygium syndrome IRF6 Variant Rett syndrome FOXG1 Wolfram syndrome WSF1 Miscellaneous Abnormal X-inactivation pattern AR Abnormal X-inactivation Alveolar capillary dysplasia FOXF1 Central diabetes insipidus AVP ** Sufficient numbers of family member, especially the blood sample of the index patient must be available before the start of a linkage analysis, judged by the Clinical Molecular Geneticist. End of the Laboratory User Guides Next version will be available in July 2016 Page 10 of 10