MOLECULAR GENETIC ANALYSES Male (DNA Analyses) Female

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Center for Human Genetics Ingelheim Konrad-Adenauer-Str. 17 55218 Ingelheim, Germany Physician Phone +49-6132-781-433, -203, -224, -165 or -578 Fax +49-6132-781-298 or -236 E-mail: [email protected] [email protected] Website: www.bioscientia.com

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In our lab we offer different testing panels by Next-Generation Sequencing (NGS). The spectrum covered by these panels is being extended constantly. For further information, please contact us (+49 6132-781-433).

Declaration of Informed Consent I agree that my test results will not be destroyed after 10 - Please delete as appropriate - With my signature, I declare that I was briefed on years (as is requested by law) to allow my family access to them in the event of my death. Place, date: _____._____._____ I consent to the results of the tests being made available to the following persons in addition to the doctor who submitted ______them: (physician) Name of patient / legal representative: about the nature, importance and implications of the ______genetic test and that I give my consent to the following I hereby agree to the transfer, in accordance with § 950 BGB, ______genetic analysis and to the collection of the blood or of any test material remaining at the end of the analysis to the tissue samples needed for this purpose: laboratory that carried out the analysis and I consent to its Signature of patient / legal representative: use for scientific purposes in pseudoanonymized form. ______I consent to the communication of my data to a medical bil- ______I consent to the storage, in accordance with legal ling clearing house for invoicing purposes. requirements, of the recorded data in paper and/or I am aware that I may withdraw this consent at any time, ver- electronic form and to their use and/or publication in bally or in writing, without giving reasons and without this pseudoanonymized form for scientific purposes for having any adverse consequences for me. quality assurance. 04.2013 · Reproduction prohibited. 5-13-0623 j

This label should be stuck onto the attached copy and kept for your Copyright bioscientia records. DO NOT SEND TO US. specimen material specimen material specimen material specimen material specimen material specimen material Copyright bioscientiaj 04.2013 · Reproduction prohibited. · 5-13-0623 All genesanalysedbyNGScanstillbeexaminedconventionalSanger-sequencing (seebelow). MOLECULAR GENETICANALYSES (inalphabeticalorder) NEXT-GENERATION SEQUENCING(NGS)PANELS A Deafness panels Eye (retinal)panels SANDD syndrome Jervell- andLange-Nielsensyndrome, Usher syndrome Deafness, X-linked Deafness, autosomalrecessive Deafness, autosomaldominant Senior-Loken syndrome Cone-rod dystrophy Retinitis pigmentosa,autosomalrecessive Retinitis pigmentosa,autosomaldominant Leber congenitalamaurosis(LCA) Aristaless-gene-related disorders* deficiency* Argininosuccinate synthetase Argininosuccinate lyasedeficiency* Arginase deficiency* Apparent mineralcorticoidexcess Apolipoprotein E Apolipoprotein B Apert syndrome(seeCraniosynostosis) Antley-Bixler syndrome* Anonychia Aniridia Angiotensin Iconvertingenzyme Angelman syndrome Androgen insensitivitysyndrome* Andersen-Tawil syndrome Alzheimer disease* Alstrom syndrome X-linked Alport syndrome Alport-like syndrome(Epstein/Fechtner) Alpha thalassemia* (Fabry disease) Alpha galactosidaseAdeficiency Alpha-1 antitrypsindeficiency Alkaptonuria* Alexander disease* Albright syndrome* Alagille syndrome Agammaglobulinemia, X-linked* Afibrinogenemia, congenital* Adrenoleukodystrophy due to21-hydroxylasedeficiency Adrenal hyperplasia,congenital, (see polycystickidneydisease) ADPKD cystic kidneydisease) (Autosomal dominantmedullary ADMCKD Acute myeloidleukemia*(AML) Acute lymphoblasticleukemia*(ALL) type Maroteaux Acromesomelic dysplasia, Acromesomelic dysplasia,typeGrebe Achondroplasia Achondrogenesis, type2 Array-CGH (specificformavailable) sequence analysisUBE3A microsatellite analysisUPD(15)pat methylation analysisSNRPN familial, type3 familial, type1 autosomal dominant autosomal recessive, COL4A3, COL4A4 FGA, FGB,FGG PKD1, PKD2 Gene(s) SERPINA1 HSD11B2 CYP21A2 COL4A5 COL2A1 SNRPN CDMP1 ALMS1 ABCD1 UBE3A RSPO4 KCNJ2 PSEN1 UMOD FGFR3 GNAS APOB MYH9 APOE NPR2 ARG1 GFAP ASS1 JAG1 PAX6 HBA HGD ARX APP ACE BTK GLA ASL AR Kidney/Liver panels B Skeletal/Connective tissuepanels C 000000000001 Filamin diseases Osteopetrosis, autosomalrecessive Osteogenesis imperfecta Ehlers-Danlos syndrome Marfan syndromeandrelateddiseases Polycystic liverdiseases(PCLD) DDD/MPGN Hemolytic uremicsyndrome(aHUS)/ Alport syndrome Focal segmentalglomerulosclerosis(FSGS) Nephrotic syndrome(SRNS) Renal tubulardysgenesis(RTD) Renal hypo-/dysplasia/agenesis/CAKUT Senior-Loken syndrome UMOD-related disorders Nephronophthisis (NPHP)/ (ADPKD/ARPKD) Polycystic kidneydiseases Ataxia, autosomaldominant Arylsulfatase Adeficiency* Arthrogryposis multiplexcongenita* (see polycystisckidneydisease) ARPKD decarboxylase deficiency* Aromatic L-aminoacid Ceroid lipofuscinosis, neural(alltypes) Catechol-O methyltransferaseactivity transferase IIdeficiency* Carnitine palmitoyl transferase Ideficiency* Carnitine palmitoyl Carnitine deficiency*,systemicprimary Canavan syndrome* Campomelic dysplasia* CADASIL Byler disease Butyrylcholinesterase deficiency* Burkitt lymphoma* Brugada syndrome Breast/Ovarian cancer* Brachydactyly typeC BOR syndrome (Sister ChromatidExchange(SCE)) Bloom syndrome* (Incontinentia pigmenti,IP2) Bloch-Sulzberger syndrome* Beta thalassemia* Beckwith-Wiedemann syndrome BCR/ABL (chronicmyeloidleukemia) Bardet-Biedl syndrome Bannayan-Riley-Ruvalcaba syndrome* Azoospermia* syndrome type1* Autoimmune polyendocrine liferative syndrometype1A* Autoimmune lymphopro- Auditory neuropathy (Tetrahydropterin, BH4-Mangel) Atypical PKU* Ataxia teleangiectasia* Ataxia withoculomotorapraxia1* Vitamin Ataxia withisolated sequence analysisCDKN1C microsatellite analysisUPD(11)pat KvDMR1 andH19-DMR methylation analysis

E deficiency* 1,3 1,2,3 SCA3, SCA6,SCA7,SCA17 3 BRCA1, BRCA2 TPM2, TNNI2 SCA1, SCA2, Gene(s) Gene(s) BCR/ABL TNFRSF6 SLC22A5 CDKN1C NOTCH3 RECQL3 ATP8B1 CDMP1 SCN5A PKHD1 USP9Y IKBKG COMT ARSA ASPA BCHE APTX PTEN SOX9 TTPA CPT2 CPT1 AIRE MYC ATM HBB DDC Other NGS-panels Other ciliopathypanels D MODY diabetes Alport syndrome Tuberous Sclerosis(TSC) Neurofibromatosis (NF) Kartagener syndrome Primary ciliarydyskinesia(PCD)/ Filamin diseases Sensenbrenner syndrome(CED) Ellis-van-Crefeld syndrome(EVC) Jeune syndrome(ATD) Meckel-Gruber syndrome Joubert syndrome Alstrom syndrome Bardet-Biedl syndrome/ Cystic fibrosis Cystinuria* Cystinosis* (see Craniosynostosis) Crouzon syndrome Crigler-Najjar syndrome FGFR associated Craniosynostosis, Cranioectodermal dysplasia Cowden syndrome* Coumarin resistance Costello syndrome* (see Joubertsyndrome) CORS syndrome Cornelia-De-Lange syndrome* Corneal dystrophy glycosylation type1a* Congenital disorderof Colon carcinoma Cockayne syndrome* Coats disease* (see Joubertsyndrome) COACH syndrome Clubbing ofdigits Cleidocranial dysplasia CINCA syndrome Ciliary dyskinesia,primary Chronic lymphaticleukemia(CLL) Chorea Huntington* Chondrodysplasia typeGrebe Chloride diarrhea,familial* CHARGE syndrome Desbuquois syndrome Denys-Drash syndrome Dentato-Rubro-Pallido-Luysiane atrophy* Deafness, autosomaldominant DNFB1 DNFB1 Deafness, autosomalrecessive Cytochrom P450defects (see polycystickidneydisease) Cystic kidneydisease Middle-East-Panel familial adenomatous poliposis coli, familial (HNPCC)* non polyposisassociated, Pendred syndrome most commonmutationswithOLA 3 FGFR1, FGFR2,FGFR3 1,2,3 1,2,3 SLC26A4, FOXI1 ERCC8, ERCC6 APC, MUTYH MLH1, MSH2 GJB6/Cx30 GJB2/Cx26 Gene(s) SLC26A3 VKORC1 UGT1A1 CDMP1 DNAH5 RUNX2 CANT1 NLRP3 PMM2 DNAI1 NIPBL HPGD HRAS CTNS PTEN CHD7 ATN1 CFTR IgVH NDP DCN WT1 HTT Diabetes, (MODY) 3 Hyperkalemic periodic paralysis SCN4A Methylentetrahydrofulate MTHFR Maturity Onset Diabetes of the Young Hyperoxaluria, primary reductase Diabetes insipidus Hyperthyroidism, TSHR Methylmalonic aziduria* MUT Diabetes mellitus, neonatal with GLIS3 familial, non autoimmune Meulengracht syndrome UGT1A1 congenital hypothyroidism Hypochondroplasia FGFR3 Mikrosatellite analysis (maternal Diamond-Blackfan anemia* RPS19 Hypokalemic periodic paralysis CACNA1A, SCN4A contamination of fetal specimen) Dihydropteridine reductase deficiency* QDPR Hypophosphatasia, infantile* ALPL Mitochondrial complex II deficiency* SDHA DPD deficiency DPYD Hypophosphatemia* Mitochondrial DNA depletion syndrome* (Dihydropyrimidine dehydrogenase deficiency) autosomal dominant FGF23 Molybdenum cofactor deficiency* Dravet syndrome SCN1A X-linked PHEX Morbus Crohn CARD15 Dysautonomia, familial IKBKAP Hypothyroidism TSHR (CARD15 polymorphism) (Riley-Day syndrome) Hypoventilation syndrome PHOX2B Morbus Fabry GLA Dyserythropoietic anemia GATA1 Morbus Gaucher* GBA with thrombocytopenia* I Gene(s) Morbus Gilbert UGT1A1 Dysfibrinogenemia, congenital 3 FGA, FGB, FGG Idiopathic short stature SHOX (UGT1A1 promotor, TA insertion) Dystonia (DOPA responsive) GCH1, TH Insulin-like growth factor 1 IGF1 Morbus Krabbe* GALC Dystonia (torsion 1, autosomal dominant) DYT1 deficiency (IGF deficiency) Morbus Meulengracht UGT1A1 Immunodeficiency, JAK3 Morbus Osler* E Gene(s) severe, combined, autosomal recessive, Morbus Pompe* GAA Ehlers-Danlos syndrome 1 T-cell neg., B-cell pos., NK-cells neg. Morbus Wilson ATP7B Ectodermal dysplasia type 1* EDA Ivemark syndrome 2 NPHP3 MORM syndrome INPP5E Ektrodactyly (EEC syndrome)* TP63 Muckle-Wells syndrome NLRP3 Ellis-van-Creveld syndrome EVC1, EVC2 J Gene(s) Muenke syndrome Epilepsies Jervell- and Lange-Nielsen syndrome (see Craniosynostosis) Epidermolysis bullosa Jeune syndrome 1,2,3 Mucolipidosis* GNPTAB Ewing sarcoma, t(11;22) translocation* EWS Joubert syndrome 1,2,3 Mucopolysaccharidosis* Multi drug resistance* F Gene(s) K Gene(s) Multiple exostosis* EXT1, EXT2 Fabry disease GLA Kabuki syndrome MLL2 Muscular dystrophies Factor II deficiency FII Kallmann syndrome 1,3 Myasthenia syndrome*, CHRNE, CHAT Factor V Leiden mutation FV Kartagener syndrome congenital combined with AChR deficiency Factor V- and Factor VIII deficiency, LMAN1 (see ciliary dyskinesia, primary) Mycobacteriosis*, IFNGR1, IFNGR2 combined Kearns-Sayre syndrome* MTTL2 familial atypical Factor X deficiency FX Kell incompatibility* KEL Myeloproliferative disorders JAK2 Familial mediterranean fever (FMF) MEFV Kniest dysplasia COL2A1 Myoclonic epilepsy Fanconi anemia* severe of infancy SCN1A Fatty acid oxidation disorder L Gene(s) Unverricht-Lundborg CSTB (acylcarnitine profile)* Lafora syndrome EPM2A, NHLRC1 Myotonia congenita* CLCN1 Feingold syndrome* MYCN Lactose intolerance, congenital LCT Myotonic dystrophy Fragile X syndrome FMR1 Langer, mesomelic dysplasia SHOX type 1 DMPK Fraser syndrome* FRAS1, FREM2 Laron syndrome GHR type 2 PROMM Frasier syndrome WT1 Larsen syndrome Myotubular myopathy,* MTM1 Friedreich ataxia* FXN FLNB X-linked Fructose intolerance, hereditary ALDOB CHST3 Fructose-1,6-bisphosphatase-deficiency* FBP1 Lathosterolosis* SC5DL N Gene(s) FSGS 1,3 Leber congenital amaurosis (LCA) 1,2,3 N-acetyl glutamate synthetase NAGS (fokal segmental glomerulosclerosis) Leber hereditary opticus mtDNA deficiency* neuropathy (LHON) N-acetyltransferase 2 deficiency NAT2 G Gene(s) LEOPARD syndrome PTPN11 Nail-Patella syndrome LXM1B Galactosemia* GALT Leri-Weil syndrome SHOX NARP syndrome* MTATP6 Gaucher disease* GBA Lesh-Nyhan syndrome HPRT1 NDH syndrome GLIS3 Glaucoma* Leukocyte adhesion deficiency Neoplasia, multiple endocrine Glomerulosclerosis, type 1 ITGB2 type 1* MEN1 fokal segmental (FSGS) 1,3 type 2 SLC35C1 type 2A RET Glucocorticoid deficiency MC2R, MRAP Li-Fraumeni syndrome* p53 type 2B RET Glucose-6-phosphatdehydrogenase- G6PD Liddle syndrome* SCNN1B, SCNN1G Nephropathy, UMOD deficiency Lissencephaly* familial, juvenile, hyperuricemic Glucose transport defect* SLC2A1 Loeys-Dietz syndrome TGFBR1, TGFBR2 Nephronophthisis 1,2,3 Glutaric acidemia type 1* GCDH Long QT syndrome Nephrotic syndrome1,2,3 Glutathione S-transferase defects* Romano-Ward syndrome 3 Netherton syndrome SPINK5 Glycerol kinase deficiency* GK Jervell- and Lange-Nielsen syndrome Neurofibromatosis Glycogen storage diseases* 1 Andersen-Tawil syndrome type 1 NF1 Granulomatosis, chronic* Timothy syndrome type 2 NF2 Greig syndrome GLI3 Lowe syndrome* OCRL1 Neuropathies 1,2,3 Gusher syndrome POU3F4 Lymphohistiocytosis*, Neutropenia*, ELA2 hemophagocytic, familial congenital, autosomal dominant H Gene(s) Lymphoma* BCL2 Nevoid basal cell carcinoma 3* Haemophilia A* FVIII Lymphedema type 1* FLT4 Nieman-Pick disease* Haemophilia B* FX Non small cell lung cancer* EGFR Hallervorden-Spatz disease PANK2 M Gene(s) Noonan syndrome PTPN11, SOS1 Hemochromatosis HFE Mantle cell lymphoma* BCL1 Norrie syndrome* NDP Hemolytic uremic syndrome (HUS) 1,2,3 Marfan syndrome HIV susceptibility* CCR5, CCR2, CXCL12 type 1 FBN1 O Gene(s) HNF1-b disease (see RCAD) TCF/HNF1b type 2 TGFBR1, TGFBR2 Obesity MC4R Holocarboxylase synthetase deficiency HLCS MASA syndrome* L1CAM Oculocutaneous albinism* Holoprosencephaly* Meckel-Gruber syndrome 1,2,3 type 1A, type 1B TYR Homocystinuria* CBS Mediterranean fever, familial (FMF) MEFV type 2 OCA2 HPA-1 genotyping* HPA1 Melanoma* CMM2, CDKN2A Onedine syndrome PHOX2B Hydroxymethylbilane synthase* HMBS MELAS syndrome* Ophthalmoplegia* 04.2013 · Reproduction prohibited. 5-13-0623

j Hyperaldosteronism, familial type 1* CYP11B1, CYP11B2 Menkes syndrome* ATP7A Optic athropy OPA1 Hypercholesterinemia MERRF syndrome* Ornithine transcarbamylase OTC Hypereosinophilic syndrome* FIP1L1, PDGFRA Metaphyseal chondrodysplasia COL10A1 deficiency* Hyperekplexia (KOK disease)* GLRA1 (Schmid type) Orofaciodigital syndrome 1 OFD1 Hyper-IgD syndrome MVK hot spot analysis Osteogenesis imperfecta Hyper-IgM syndrome* CD40LG complete gene analysis incl. hot spots Osteogenesis imperfecta,

160065170075 Osteopetrosis,* Silver-Rusell syndrome X-linked sideroblastic anemia and ABCB7 autosomal recessive methylation analysis Ataxia* Osteoporosis COL1A1, VDR KvDMR1 and H19DMR Otopalatodigital syndrome FLNA microsatellite analysis UDP(7)mat type 1 (OPD1) Sjögren-Larsson syndrome* ALDH3A2 Others type 2 (OPD2) Smith-Lemli-Opitz syndrome* DHCR7 Melnick-Needles syndrome (MNS) Sotos syndrome NSD1 frontometaphyseal dysplasia (FMD) Spastic paraplegia 3 Spinal bulbar muscular atrophy*, AR P Gene(s) type Kennedy PAI gene analysis PAI1 Spinal muscular atrophy (SMA) SMN1 Pancreatitis, PRSS1, SPINK1, CFTR Spinocerebellar ataxia 3 hereditary Spondylocostal dysostosis* DLL3 Paramyotonia congenita, SCN4A Spondyloepiphyseal dysplasia COL2A1 of von Eulenberg Spondyloepiphyseal dysplasia, SEDL Parkinson disease* X-linked Pelizaeus-Merzbacher disease* PLP Sterility CFTR Peutz-Jeghers syndrome* STK11 (Congenital aplasia of vas deferens) Pfeiffer syndrome Stickler syndrome type 1 COL2A1 (see Craniosynostosis) Succinate dehydrogenase SDHB, SDHD Phenylalanine hydroxylase deficiency* PAH deficiency* Pierson syndrome LAMB2 Surfacant dysfunction PKD1/TSC 2 microdeletion syndrome pulmonary 1 SFTPB Polyposis coli, APC, MUTYH pulmonary 3* ABCA3 familial adenomatous (FAP) pulmonary 4* CSF2RB Polysyndactyly* HOXD13 Polycystic kidney disease 1,2,3 T Gene(s) autosomal dominant (type 1) PKD1 Tay-Sachs disease autosomal dominant (type 2) PKD2 Jewish sreening HEXA autosomal recessive PKHD1 complete gene HEXA Polycystic kidney disease, PKD1/TSC2 HEXA and HEXB genes HEXA, HEXB severe infantile, with tuberous sclerosis T-cell receptor-g rearrangement* Pontocellebar hypoplasia type 1 VRK1 Thanatophoric dysplasia FGFR3 Prader-Willi syndrome SNRPN Thiopurine methyltransferase TPMT methylation analysis deficiency SNRPN gene Thrombophilia MTHFR microsatellit analysis UPD(15)mat Thrombotic ADAMTS13 Primary ciliary dyskinesia thrombocytopenic purpura (TTP) DNAH5 Thyroid hormone resistance THR-beta DNAI1 Timothy syndrome CACNA1C Primary hypertrophic HPGD TNF receptor associated TNFRSF1A Osteoarthropathy periodic fever (Pachydermoperiostose/Tourraine- Treacher-Collins- TCOF1 Solente-Gole syndrome) Franceschetti syndrome* Progressive familial intrahepatic Trimethylaminuria* FMO3 cholestasis TSC2/PKD1 microdeletion syndrome Propionic acidemia* PCCA, PCCB Tuberous sclerosis Protein-C deficiency* PROC type 1 TSC1 Proteus syndrome* PTEN type 2 TSC2 Protoporphyria, erythropoietic* FECH Tyrosinemia* CD40LG Pseudoachondroplasia* COMP Pyruvate carboxylase deficiency* PC U Gene(s) Pyruvate dehydrogenase PDHA1 UMOD disease UMOD deficiency* (see ADMCKD) Uniparental disomy of R Gene(s) chromosome: 3 2, 4, 6, 7, 11, 13, 14, 15, 16 RCAD TCF/HNF1b Usher syndrome 1,2,3 (Renal Cyst and Diabetes syndrome) type 1 Renal agenesis/dysplasia TCF/HNF1b, RET type 2 Renal cell carcinoma MET USH1: FC-/Acadian Panel Renal-Coloboma syndrome PAX2 USH2: FC-/Acadian Panel Renal cysts (see polycystic kidney disease) V Gene(s) Renal-tubular dysgenesia 1,2,3 Very long chain acyl-CoA ACADVL Retinitis pigmentosa 1,2,3 dehydrogenase deficiency* autosomal dominant Vitamin D resistant rachitis* autosomal recessive Vitreoretinopathy, TSPAN12, NDP Retinoblastoma RB1 familial exsudative* Retinoschisis RS1 Von Hippel-Lindau syndrome VHL Rett syndrome MECP2 von Willebrand disease* VWF Rhesus-(Rh) compatibility* RHCE RHCE W Gene(s) RHD RHD Waardenburg syndrome 2,3 Romano-Ward syndrome 3 Warfarin or Coumarin sensitivity* VKORC1 Rubinstein-Taybi syndrome* CREBBP Weaver syndrome NSD1 Werner syndrome RECQL2 S Gene(s) Wilms tumor WT1 Sandhoff disease HEXB Wiskott-Aldrich syndrome* WAS Schinzel-Giedeon syndrome SETBP1 Wolfram syndrome type 2 CISD2 04.2013 · Reproduction prohibited. 5-13-0623 1,2,3 j Senior-Loken syndrome Sensenbrenner syndrome X Gene(s) Septooptic dysplasia* HESX1 Xanthinuria XDH SESAME syndrome KCNJ10 X-linked hydrocephalus* L1CAM Shwachman-Diamond syndrome* SBDS X-linked lymphproliferative SH2D1A Sialuria* SLC17A5 syndrome*

000000000001 Copyright bioscientiaj 04.2013 · Reproduction prohibited. · 5-13-0623 MOLECULAR GENETICANALYSES (bydiseasegroups) Cancer/Leukemia/Tumor Blood disorders Dysfibrinogenemia, congenital with thrombocytopenia* Dyserythropoietic anemia Diamond-Blackfan anemia* Beta thalassemia* Alpha thalassemia* congenital* Afibrinogenemia, lymphoproliferative syndrome* X-linked Wilms tumor Von Hippel-Lindausyndrome Tuberous sclerosis Shwachman-Diamond syndrome* Retinoblastoma Renal cellcarcinoma Proteus syndrome* Peutz-Jeghers syndrome* Non smallcelllungcancer* Nevoid basalcellcarcinoma Neurofibromatosis Neoplasia, multipleendocrine Myeloproliferative disorder Melanoma* Mantle celllymphoma* Lymphoma* Li-Fraumeni syndrome* Fanconi anemia* t(11;22) translocation* Ewing sarcoma, Cowden syndrome* Colon carcinoma Chronic lymphaticleukemia(CLL)* Burkitt lymphoma* Breast/Ovarian cancer* (Sister ChromatidExchange(SCE)) Bloom syndrome* (chronic myeloidleukemia) BCR/ABL Ruvalcaba syndrome* Bannayan-Riley- Ataxia teleangiectasia* Acute myeloidleukemia*(AML) Acute lymphoblasticleukemia*(ALL) Ataxia* X-linked sideroblasticanemiaand X-linked sideroblasticanemia* Wiskott-Aldrich syndrome* Warfarin orCoumarinsensitivity* von Willebranddisease* thrombocytopenic purpura(TTP) Thrombotic Thrombophilia Sickle cellanemia RHCE RHD Rhesus (Rh)incompatibility* PAI geneanalysis congenital, autosomaldominant Neutropenia*, Kell incompatibility* HPA-1-genotyping* Haemophilia B* Haemophilia A* Factor Xdeficiency combined Factor V- andFactorVIIIdeficiency, Factor V-Leiden mutation Factor IIdeficiency type 2 type 1 type 2 type 1 type 2B type 2A type 1* familial adenomatous poliposis coli, familial (HNPCC)* non polyposisassociated, 3 * 3 CMM2, CDKN2A BRCA1, BRCA2 FGA, FGB,FGG FGA, FGB,FGG APC, MUTYH MLH1, MSH2 ADAMTS13 Gene(s) Gene(s) BCR/ABL METHFR VKORC1 SH2D1A RECQL3 LMAN1 ABCB7 ALAS2 GATA1 RPS19 STK11 MEN1 SBDS PTEN RHCE PTEN PTEN HPA1 JAK2 EGFR TSC2 TSC1 BCL1 BCL2 WAS ELA2 EWS IgVH MYC VWF ATM PAI1 FVIII HBB HBA HBB WT1 MET RHD VHL RB1 RET RET NF2 NF1 KEL p53 FX FX FV FII Dementia Deafness Connective tissuedisorders Chromosome instability Cardiac disorders Epigenetic disorders Endocrinology 160065170083 Long QTsyndrome Brugada syndrome Angiotensin Iconvertingenzyme Waardenburg syndrome Usher syndrome Deafness, autosomaldominant DNFB1 DNFB1 Deafness, autosomalrecessive SESAME syndrome SANDD syndrome Jervell- andLange-Nielsensyndrome Gusher syndrome BOR syndrome1,3 Auditory neuropathy Alstrom syndrome Surfacant dysfunction Ehlers-Danlos syndrome Alpha-1 antitrypsindeficiency Fanconi anemia* (Sister ChromatidExchange(SCE)) Bloom syndrome* Ataxia teleangiectasia* Beckwith-Wiedemann syndrome Angelman syndrome Wolfram syndrometype2 Vitamin Dresistentrachitis* Thyroid hormoneresistance Shwachman-Diamond syndrome* NDH syndrome Liddle syndrome Lathosterolosis* Laron syndrome Kallmann syndrome (IGF deficiency) Insulin likegrowthfactor1deficiency Hypothyroidsm familial, nonautoimmune Hyperthyroidsm, congenital* Hyperinsulinism, Glucocorticoid deficiency hypothyreodism neonatal withcongenital Diabetes mellitus, Diabetes insipidus Maturity OnsetDiabetesoftheYoung Diabetes, (MODY) Apparent mineralcorticoidexcess Androgen insensivitysyndrome* Albright syndrome* Luysiane atrophy* Dentato-Rubro-Pallido- Alzheimer disease* Romano-Ward syndrome Pendred syndrome pulmonary 4* pulmonary 3* pulmonary 1 Timothy syndrome Andersen-Tawil syndrome Jervell- andLange-Nielsensyndrome sequence analysisCDKN1C microsatellite analysisUPD(11)pat KvDMR1 andH19-DMR methylation analysis sequence analysisUBE3A microsatellite analysisUPD(15)pat methylation analysisSNRPN familial, type3 familial, type1 1,2,3 3 1,3 2,3 1 ABCC8, KCNJ11,GLUD1 3 1,2,3 1,2,3 SCNN1B, SCNN1G SLC26A4, FOXI1 MC2R, MRAP GJB6/Cx30 GJB2/Cx26 Gene(s) Gene(s) Gene(s) Gene(s) Gene(s) Gene(s) Gene(s) SERPINA1 CACNA1D THR-beta HSD11B2 CDKN1C KCNJ10 CSF2RB RECQL3 POU3F4 SNRPN ALMS1 SCN5A ABCA3 UBE3A PSEN1 SFTPB SC5DL CISD2 GNAS SBDS GLIS3 GLIS3 TSHR TSHR ATN1 ATM GHR IGF1 APP ACE AR Eye (retinal)disorders Epilepsy Immune systemdisorders Gastroenterologic disorders Bardet-Biedl syndrome Aniridia Alstrom syndrome Unverricht-Lundborg Myoclonic epilepsy Lafora syndrome Epilepsies Aristaless-gene-related disorders* Usher syndrome Retinoschisis Retinitis pigmentosa Ophthalmoplegia* Oculocutaneous albinism* Norrie syndrome* Lowe syndrome* neuropathy (LHON) Leber hereditaryoptic Leber congenitalamaurosis(LCA) Joubert syndrome Glaukoma* Corneal dystrophy Congenital stationarynightblindness Coats disease* chromosome: Uniparental disomyof Silver-Rusell syndrome Prader-Willi syndrome Leukocyte adhesiondeficiency T-cell neg.,B-cellpos.,NK-cells neg. severe, combined;autosomalrecessive, Immunodeficiency, Hyper-IgM syndrome* Hyper-IgD syndrome syndrome* Hypereosinophilic Granulomatosis, chronic* (Sister ChromatidExchange(SCE)) Bloom syndrome* syndrome type1A* Autoimmune polyendocrine syndrome type1* Autoimmune lymphoproliferative Agammaglobulinemia, X-linked* Cholestasis Progressive familialintrahepativ familial adenomatous(FAP) Polyposis coli, Peutz-Jeghers syndrome* hereditary Pancreatitis, Morbus Gilbert (CARD15 polymorphism) Morbus Crohn Middle-East-Panel Cystic fibrosis Crigler-Najjar syndrome Chloride diarrhea,familial* Byler disease Alagille syndrome familial exsudative* Vitreoretinopathy, (see Ushersyndrome) severe, ofinfancy autosomal recessive autosomal dominant type 2 type 1A,1B microsatellite analysisUDP(7)mat KvDMR1 andH19DMR methylation analysis microsatellit analysisUPD(15)mat SNRPN gene methylation analysis type 2 type 1 most commonmutationswithOLA 3 3 2,4,6,7,11,13,14,15,16 1,2,3 1,2,3 1,2,3 1,2,3 PRSS1, SPINK1,CFTR 1,2,3 EPM2A, NHLRC1 FIP1L1, PDGFRA TSPAN12. NDP APC, MUTYH Gene(s) Gene(s) Gene(s) Gene(s) TNFRSF6 SLC26A3 SLC35C1 CARD15 UGT1A1 UGT1A1 RECQL3 CD40LG ATP8B1 SNRPN mtDNA ALMS1 SCN1A OCRL1 STK11 ITGB2 CSTB OCA2 JAG1 PAX6 JAK3 CFTR MVK AIRE NDP DCN NDP ARX BTK RS1 TYP Lymphohistiocytosis*, Tuberous sclerosis Dihydropteridine reductase QDPR hemophagocytic, familial type 1 TSC1 deficiency Lymphoma* type 2 TSC2 DPD deficiency DPYD Muckle-Wells syndrome NLRP3 TSC2/PKD1 microdeletion syndrome (Dihydropyrimidindehydrogenase deficiency) Neutropenia*, ELA2 UMOD disease (see ADMCKD) UMOD Fatty acid oxidation disorder congenital, autosomal dominant (Acylcarnitine profile)* Makrosomia/Giantism T-cell receptor-g rearrangement* Gene(s) Fructose intolerance, hereditary ALDOB Beckwith-Wiedemann syndrome Fructose-1,6-bisphosphatase- FMP1 Infection Gene(s) methylation analysis deficiency* HIV susceptibility* CCR5, CCR2, CXCL12 KvDMR1 and H19-DMR Glucose-6 phosphat G6PD Mycobacteriosis*, IFNGR1, INFGR2 microsatellite analysis UPD(11)pat dehydrogenase deficiency familial atypical sequence analysis CDKN1C CDKN1C Glucose transport defect* SLC2A1 Sotos syndrome NSD1 Glutaric acidemia type 1* GCDH Infertility Gene(s) Weaver syndrome NSD1 Glutathione S-transferase defects* Azoospermia* USP9Y Glycerol kinase deficiency* GK Cystic fibrosis 3 CFTR Malformation syndromes Gene(s) Holocarboxylase synthetase HLCS most common mutations with OLA Alagille syndrome JAG1 deficiency* Middle-East-Panel Alstrom syndrome ALMS1 Homocystinuria* CBS Kallmann syndrome 1,3 Antley-Bixler syndrome* Hydroxymethylbilane synthase* HMBS Kartagener syndrome Bardet-Biedl syndrome 1,2,3 Hyperaldosteronism, CYP11B1, CYP11B2 (see primary ciliary dyskinesia) BOR syndrome 1,3 familial type 1* Primary ciliary dyskinesia CHARGE syndrome CHD7 Hypercholesterinemia DNAH5 COACH syndrome Lactose intolerance, congenital LCT DNAI1 (see Joubert syndrome) Methylentetrahydrofulate reductase MTHFR Sterility CFTR Cornelia-De-Lange syndrome* NIPBL Methylmalonic aciduria* MUT (congenital aplasia of vas deferens) CORS syndrome Meulengracht syndrome UGT1A1 (see Joubert syndrome) Molybdenum cofactor deficiency* Inflammation Gene(s) Costello syndrome* HRAS Morbus Gaucher* GBA CINCA syndrome NLRP3 Denys-Drash syndrome WT1 Morbus Gilbert UGT1A1 Familial mediterranean fever (FMF) MEFV Ellis-van-Creveld syndrome EVC1, EVC2 (UGT1A1promotor, TA insertion) Hyper-IgD syndrome MVK Feingold syndrome* MYCN Morbus Krabbe* GALC TNF receptor associated TNFRSF1A Greig syndrome GLI3 Morbus Meulengracht UGT1A1 periodic fever Ivemark syndrome 2 NPHP3 Morbus Osler* Jeune syndrome 1,2,3 N-acetyl glutamate synthetase NAGS Kidney disorders Gene(s) Joubert syndrome 1,2,3 deficiency* ADMCKD UMOD LEOPARD syndrome PTPN11 Obesity MC4R (autosomal dominant medullary Meckel-Gruber syndrome 1,2,3 Ornithine transcarbamylase OTC cystic kidney disease) MORM syndrome INPP5E deficiency* ADPKD PKD1, PKD2 Orofaciodigital syndrome 1 OFD1 Phenylalanine hydroxylase deficiency* PAH (see polycystic kidney disease) Schinzel-Giedeon syndrome SETBP1 Propionic acidemia* PCCA, PCCB Alport-like syndrome MYH9 Smith-Lemli-Opitz syndrome* DHCR7 Protoporphyria, erythropoietic* FECH (Epstein/Fechtner) Pyruvate carboxylase deficiency* PC Alport syndrome Mental retardation Gene(s) Pyruvate dehydrogenase PDHA1 X-linked COL4A5 Alexander disease* GFAP deficiency* autosomal recessive, COL4A3, COL4A4 Angelman syndrome Sialuria* SLC17A5 autosomal dominant methylation analysis SNRPN SNRPN Smith-Lemli-Opitz syndrome* DHCR7 Alstrom syndrome ALMS1 microsatellite analysis UPD(15)pat Succinate dehydrogenase SDHB, SDHD ARPKD PKHD1 sequence analysis UBE3A UBE3A deficiency* (see polycystic kidney disease) Antley-Bixler syndrome* Thiopurine methyltransferase TPMT Bardet-Biedl syndrome 1,2,3 Aristaless-gene-related disorders* ARX deficiency* BOR syndrome 1,3 Canavan syndrome* ASPA Trimethylaminuria* FMO3 Cystinosis* CTNS Fragile X syndrome FMR1 Tyrosinemia* CD40LG Denys-Drash syndrome WT1 Fraser syndrome* FRAS1, FREM2 Very long chain acyl-CoA ACADVL Diabetes insipidus Holoprosencephaly* dehydrogenase deficiency* Frasier syndrome WT1 Kabuki syndrome MLL2 Xanthinuria XDH Glomerulosclerosis, Lissencephaly* fokal segmental (FSGS) 1,3 Rett syndrome MECP2 Mitochondriopathies Gene(s) Hemolytic uremic syndrome (HUS) 1,3 Kearns-Sayre syndrome* MTTL2 Metabolic disorders HNF1-b disease (see RCAD) TCF/HNF1b Gene(s) Leber hereditary opticus mtDNA Hyperoxaluria, primary Adrenal hyperplasia, congenital, CYP21A2 neuropathy (LHON) Ivemark syndrome 2 NPHP3 due to 21-hydroxylase deficiency MELAS syndrome* Joubert syndrome 1,2,3 Alkaptonuria* HGD MERRF syndrome* Meckel-Gruber syndrome 1,2,3 Alpha galactosidase deficiency GLA Mitochondrial complex II deficiency* SDHA Morbus Fabry GLA (Morbus Fabry) Mitochondrial DNA depletion syndrome* Nail-Patella syndrome LMX1B Apolipoprotein B APOB Nephropathy, UMOD Apolipoprotein E APOE Neuromuscular disorders Gene(s) familial, juvenile hyperuricemic Arginase deficiency* ARG1 Muscular dystrophies Nephronophthisis 1,2,3 Argininosuccinate lyase deficiency* ASL Myotonia congenita* CLCN1 Nephrotic syndrome 1,2,3 Argininosuccinate synthetase ASS1 Myotonic dystrophy Orofaciodigital syndrome 1 OFD1 deficiency* type 1 DMPK PKD1/TSC 2 microdeletion syndrome Aromatic L-aminoacid DDC type 2 PROMM Polycystic kidney disease 1,2,3 decarboxylase deficiency* Myotubular myopathy,* X-linked MTM1 autosomal dominant (type 1) PKD1 Atypical PKU* Paramyotonia congenita, SCN4A autosomal dominant (type 2) PKD2 (Tetrahydropterin, BH4 deficiency) of von Eulenberg autosomal recessive PKHD1 Butyrylcholinesterase deficiency* BCHE Polycystic kidney disease, PKD1/TSC2 Carnitine deficiency*, SLC22A5 Neurology/Neuropathies Gene(s) severe infantile, with tuberous sclerosis systemic primary Ataxia, autosomal dominant 3 SCA1, SCA2, RCAD TCF/HNF1b Carnitine palmitoyl CPT1 SCA3, SCA6, SCA7, SCA17 (Renal Cysts and Diabetes syndrome) transferase I deficiency* Ataxia with isolated TPPA 04.2013 · Reproduction prohibited. 5-13-0623

j Renal agenesis/dysplasia TCF/HNF1b, RET Carnitine palmitoyl CPT2 Vitamin E deficiency* Renal-Coloboma syndrome PAX2 transferase II deficiency* Ataxia with oculomotor apraxia 1* APTX Renal cysts Catechol-O methyltransferase COMT Ataxia teleangiectasia* ATM (see polycystic kidney disease) activity Chorea Huntington* HTT Renal-tubular dysgenesis 1,2,3 Congenital disorder of PMM2 Dentato-Rubro-Pallido- ATN1 Senior-Loken syndrome 1,2,3 glycosylation type 1a* Luysiane atrophy*

000000000001 Copyright bioscientiaj 04.2013 · Reproduction prohibited. · 5-13-0623 Skeletal disorders Short stature Pharmacogenetics Spastic paraplegies Smith-Lemli-Opitz syndrome* Rett syndrome Pontocellebar hypoplasiatype1 Pelizaeus-Merzbacher disease* Parkinson disease* Onedine syndrome Hypophosphatasia, infantile* Hypochondroplasia Ektrodactyly (EECsyndrome)* Desbuquois syndrome Cystinuria* Crouzon syndrome(seeCraniosynostosis) FGFR associated Craniosynostosis, Cranioectodermal dysplasia Clubbing ofdigits Cleidocranial dysplasia Chondrodysplasia, typeGrebe Campomelic dysplasia* Brachydactyly typeC congenita* Arthrogryposis multiplex Apert syndrome(seeCraniosynostosis) Albright syndrome* type Maroteaux Acromesomelic dysplasia, type Grebe Acromesomelic dysplasia, Achondroplasia Achondrogenesis type2 Silver-Rusell syndrome Noonan syndrome Leri-Weill syndrome Laron syndrome Langer, mesomelicdysplasia (IGF deficiency) Insulin likegrowthfactor1deficiency Idiopathic shortstature Costello syndrome* Cockayne syndrome* Albright syndrome* N-acetyltransferase 2deficiency Multi drugresistance* (Dihydropyrimidindehydrogenase deficiency) DPD deficiency Cytochrome P450defects X-linked hydrocephalus* Spinocerebellar ataxies Spinal muscularatrophy(SMA) type Kennedy Spinal bulbarmuscularatrophy*, Neuropathies NARP syndrome* Unverricht-Lundborg Myoklonic epilepsy congenital combinedwithAChRdeficiency Myasthenic syndrome*, Menkes syndrome* MASA syndrome* Lesh-Nyhan syndrome Lafora syndrome Hypoventilation syndrome periodic paralysis Hypokalemic Hyperkalemic periodicparalysis Hyperekplexia (KOKdisease)* Hallervorden-Spatz disease Friedreich ataxia* (torsion 1,autosomaldominant) Dystonia Dystonia (DOPA responsive) (Riley-Day syndrome) Dysautonomia, familial microsatellite analysisUDP(7)mat KvDMR1 andH19DMR methylation analysis severe ofinfancy 1,2,3 3 3 FGFR1, FGFR2,FGFR3 CACNA1A, SCN4A EPM2A, NHLRC1 PTPN11, SOS1 ERCC8, ERCC6 CHRNE, CHAT TPM2, TNNI2 Gene(s) Gene(s) Gene(s) GCH1, TH PHOX2B PHOX2B MTATP6 SCN11A IKBKAP COL2A1 CDMP1 CDMP1 CDMP1 MECP2 L1CAM L1CAM RUNX2 SCN4A PANK2 CANT1 DHCR7 HPRT1 GLRA1 ATP7A SMN1 FGFR3 FGFR3 GNAS GNAS HPGD SHOX SHOX SHOX HRAS DPYD NPR2 CSTB SOX9 NAT2 VRK1 ALPL DYT1 TP63 GHR IGF1 FXN PLP AR Storage disorders Skin andnaildisorders 160065170091 Glycogen storagediseases* Gaucher disease* Fabry disease (all types) Ceroid lipofuscinosis,neural Arylsulfatase Adeficiency* Werner syndrome Sjögren-Larsson syndrome* Solente-Gole syndrome) (Pachydermoperiostose/Tourraine- Osteoarthropathy Primary hypertrophic Neurofibromatosis Netherton syndrome Epidermolysis bullosa Ectodermal dysplasiatype1* (Sister ChromatidExchange(SCE)) Bloom syndrome* (Incontinentia pigmenti,IP2) Bloch-Sulzberger syndrome* Anonychia Franceschetti syndrome* Treacher-Collins- Thanatophoric dysplasia Stickler-syndrome type1 X-linked Spondyloepiphyseal dysplasia, Spondyloepiphyseal dysplasia Spondylocostal dysostosis* Shwachman-Diamond syndrome* Sensenbrenner syndrome Rubinstein-Taybi syndrome* Pseudoachondroplasia* Polysyndactyly* Pfeiffer syndrome(seeCraniosynostosis) Otopalatodigital syndrome Osteoporosis Osteopetrose,* autosomalrecessive autosomal recessive Osteogenesis imperfecta, Osteogenesis imperfecta Orofaciodigital syndrome1 Nail-Patella syndrome Multiple exostosis* (type Schmid) Metaphyseal Chondrodysplasia Marfan syndrome Loeys-Dietz syndrome Leri-Weill syndrome Larsen syndrome Langer, mesomelic dysplasia Kniest dysplasia X-linked Hypophosphatemia* dehydrogenase deficiency* Very longchainacyl-CoA Tay-Sachs disease Sandhoff disease Nieman-Pick disease* Mucopolysaccharidosis* Mucolipidosis* Morbus Wilson Morbus Pompe* Morbus Krabbe* Hallervorden-Spatz disease Hemochromatosis type 2 type 1 frontometaphyseal dysplasia(FMD) Melnick-Needles syndrome(MNS) type 2(OPD2) type 1(OPD1) complete geneanalysisincl.hotspots hot spotanalysis type 2 type 1 autosomal dominant HEXA andHEXBgenes complete gene Jewish screening 1 TGFBR1, TGFBR2 TGFBR1, TGFBR2 COL1A1, VDR HEXA, HEXB EXT1, EXT2 Gene(s) Gene(s) ALDH3A2 COL10A1 GNPTAB CREBBP ACADVL HOXD13 RECQL2 RECQL3 COL2A1 COL2A2 COL2A2 SPINK5 LMX1B PANK2 RSPO4 CHST3 ATP7B IKBKG COMP TCOF1 FGFR3 HPGD FGF23 SHOX ARSA SBDS SHOX HEXA HEXA HEXB PHEX FLNA FBN1 FLNB SEDL OFD1 DLL3 GAA GBA EDA GLA HFE NF2 NF1 Vasculopathies Usher syndrome *Analyses arecarried outincollaboratingcertifiedlabs. 3 2 1 Stepwiseanalysis We offer linkageanalysiswhereapplicable Pleasecontactus. correlationsexistthatallowfortargetedtesting. disease.Insomecases,specificgenotype-phenotype We offermoleculartestingforallgenesknownthis tested. parental consanguinity)forprioritizationof genestobe (e. g.,samplesavailablefromseveralfamily members, Lymphedema type1* CADASIL Usher syndrome USH2: FC-/AcadianPanel USH1: FC-/AcadianPanel type 2 type 1

1,2,3 Gene(s) Gene(s) NOTCH3 FLT4