Patient's SURNAME, First Name

Stamp of Physician/Clinic and/or Barcode

Prof. Elke Holinski-Feder, MD Angela Abicht, MDHuman Geneticists

Bayerstr. 3 – 5D-80335 Munich

Tel. +49 89 / 30 90 886 - 0Fax +49 89 / 30 90 886 - 66 info@mgz-muenchen.de

All forms are availablefrom our website:www.mgz-muenchen.de

AOK LKK BKK IKK VdAK AEV Knappschaft

Insurance Provider Insurance Number Status

Date of Birth

Physician Insurance valid until Today's Date

MedizinischGenetisches Zentrum

06/ 2

013

ENG

Sample date Time

Sex male female

Cost carrier: Invoice to patient Invoice to clinic E112 (European Union only)

We have been informed of and agree to the costs of the test according to the

cost estimate provided (please enclose copy).

Patient known to MGZ - Medizinisch Genetisches Zentrum? Yes No

For follow-up questions and the forwarding of test results, please indicate:

Name of attending physician and/or ward:

Telephone Telefax

Please indicate clinical diagnosis, symptoms or test results and family history:

Have any genetic tests already been performed? Yes No

If yes, which? Results?

In accordance with the German Genetic Diagnostics Act (GenDG), I consent to genetic testing corresponding to the

accompanying request and/or for the purpose of clarifying the abovementioned clinical problem(s) as well as to:

the forwarding of this request to a specialised cooperating laboratory

(if required).

No

the storage of my genetic material for new diagnostic possibilities, for

the verification of results, as well as for scientific purposes (please cross

out those options which do not apply).

No

the use of my test results in the counseling and testing of family members. No

the archiving of my test results beyond the legally regulated timespan of 10

years.

No

I consent to the forwarding of my test results to the following doctors:

This declaration of consent in accordance with the German Genetic Diagnostics Act (GenDG) is valid for me and/

or for my child and may be revoked in whole or in part at any time. I have had sufficient time to consider giving

my consent.

Date, Place Signature of patient or his / her legal representative Attending physician

Patient's name:

Chromosome Analyses Karyotype analysis of peripheral blood Karyotype analysis of amniotic fluid Karyotype analysis of chorionic (CVS) / placenta villi Karyotype analysis of umbilical cord blood Karyotype analysis of skin fibroblasts Karyotype analysis of products of conception

Molecular Karyotyping / Array-CGH Diagnostics Array-CGH diagnostics (Oligo-Array) Array-CGH diagnostics (Oligo-Array), prenatal

Molecular Cytogenetics – FISH-Diagnostics FISH aneuploidy screening (chrom. 13, 18, 21, X and Y) Trisomy 21 (blood smear) Subtelomere analysis FISH diagnostics (please indicate problem)

Sample: EDTA blood HEPARIN blood Other ! IMPORTANT : EDTA blood of parents required Diagnostics only upon prior arrangement

Cytogenetics and Molecular CytogeneticsUdo Koehler, PhD

Smith-Magenis Syndrome, Microdeletion 17p11.2 Further diagnostics: RAI1

Sotos Syndrome, NSD1 Stickler Syndrome COL2A1 COL11A1 Stüve-Wiedemann Syndrome, LIFR Thanatophoric Dysplasia, FGFR3 Weaver Syndrome, EZH2 Weill-Marchesani Syndrome ADAMTS10 ADAMTS17 X-Linked Mental Retardation, Christianson Type

(Angelman-like Syndrome), SLC9A6 X-Linked Mental Retardation,

Creatine Transporter Deficiency, SLC6A8 X-Linked Mental Retardation, XLMR, Linkage

Familial Tumor Diseases, Gastroenterology **Prof. Elke Holinski-Feder, MD; Brigitte Schönfeld, MD;Andreas Laner, PhD; Teresa Neuhann, MD

Adenomatous Polyposis APC MUTYH Analysis of tumor tissue

MLH1 promoter methylation* BRAF* KRAS* Microsatellite analysis

Birt-Hogg-Dubé Syndrome, FLCN Breast / Ovarian Cancer BRCA1 BRCA2 ATM

RAD51C RAD51D CHEK2 hotspot CHEK2 complete Carney Complex, PRKAR1A Cowden Syndrome, PHTS, PTEN Gorlin Syndrome, Nevoid Basal Cell Syndrome, PTCH1 Hemorrhagic Telangiectasia, Osler-Rendu-Weber Syndrome

ENG ACVRL1 Hereditary Papillary Renal Cell Carcinoma, MET Proto-Onkogene HNPCC, Lynch Syndrome

MLH1 MSH2 MSH6 PMS2 Juvenile Polyposis BMPR1A SMAD4 ENG Constitutional MMR Deficiency Syndrome, CMMR-D Leiomyomatosis / Renal Cell Cancer, FH Li-Fraumeni Syndrome, p53 Stomach Cancer, E-Cadherin, CDH1 Malignant Melanoma, p16 / CDKN2A Multiple Endocrine Neoplasia Type 1, MEN1, MEN1 Multiple Endocrine Neoplasia Type 2, MEN2, RET

MEN2A MEN2B Pancreatitis SPINK1 PRSS1 CFTR Pancreatic Carcinoma PALB2 p16 / CDKN2A Paraganglioma-Pheochromocytoma Syndrome

PGL1, SDHD PGL3, SDHC PGL4, SDHB Pheochromocytoma MAX TMEM127 Peutz-Jeghers Syndrome, STK11 Schwannomatosis, INI1 / SMARCB1 Von Hippel-Lindau Syndrome, VHL Wilms Tumor, WT1

Multi-Gene Panels (Next Generation Sequencing) Congenital Myasthenic Syndromes (CMS) Hereditary Neuropathies (HMSN / CMT) Mitochondrial Diseases Epileptic Encephalopathy

Detailed information available at www.mgz-muenchen.de

Mental Retardation and Dysmorphic SyndromesProf. Elke Holinski-Feder, MD; Stefanie Balg, MD;Teresa Neuhann, MD; Brigitte Schönfeld, MD

Array-CGH / MLPA Diagnostics Microdeletion / Microduplication Syndrome If applicable, specific syndrome: Autism

Achondroplasia, FGFR3 Alpha Thalassemia with mental retardation, ATRX Andermann Syndrome, ACCPN, KCC3, SLC12A6 Angelman Syndrome: Methylation test

Further diagnostics: Negative methylation test: UBE3A ! Positive methylation test: UPD15

ARX-associated diseases Partington Syndrome XLAG Syndrome X-Linked West Syndrome XMESID Syndrome

Beckwith-Wiedemann Syndrome: Methylation test Further diagnostics: Negative methylation test: CDKN1C ! Positive methylation test: UPD11

Berardinelli-Seip Congenital Lipodystrophy, BSCL2 (Exon 3) Coffin-Lowry Syndrome, RSK2 DiGeorge/ VCFS Syndrome, Microdeletion 22q11.21 Fragile X Syndrome, FMR1 Hypochondroplasia, FGFR3 Kabuki Syndrome, MLL2 Legius Syndrome, SPRED1 Marfan Syndrome, FBN1 Menkes Disease, ATP7A Mental Retardation, Hyperkinesia, Epilepsy, MEF2C Mowat-Wilson Syndrome, ZEB2 Opitz G/BBB Syndrome, MID1 Pitt-Hopkins Syndrome, TCF4 Prader-Willi Syndrome: Methylation test

Further diagnostics: ! Positive methylation test: UPD15

Rett Syndrome, MECP2 Rett Syndrome, congenital variant, FOXG1 Rett Syndrome with Infantile Epilepsy, CDKL5 Silver-Russell Syndrome: Methylation test

Further diagnostics: ! Negative methylation test: UPD 7

Molecular Genetics

**Our lab is accredited by the German National Accreditation Council (DAkkS) in accordance with DIN EN ISO/IEC 15189 and DIN EN ISO 17025 — except for those analyses marked with an asterisk (*).

In order to select the appropriate gene(s), please refer to the anamnesis forms and/or information on our website: www.mgz-muenchen.de / downloads.html

Patient's name:

Familial Infantile Epilepsy, PRRT2 Absence Epilepsy in Childhood CACNA1H SLC2A1 Unverricht-Lundborg Disease, CSTB Juvenile Myoclonic Epilepsy, EFHC1 POLG-associated Epilepsy, POLG

Migraine / Channel Diseases / Paroxysmal Neurological DisordersAngela Abicht, MD; Prof. Bernd Rautenstrauss, ScD

Familial Hemiplegic Migraine (FHM) CACNA1A (FHM1) ATP1A2 (FHM2) SCN1A (FHM3)

Alternating Hemiplegia of Childhood, ATP1A3 Episodic Ataxia Type 2, CACNA1A Ondine Syndrome, PHOX2B Periodic Paralysis SCN4A CACNA1S Paroxysmal Kinesigenic Dyskinesia, PRRT2 Paroxysmal Exertion-induced Dystonia, DYT18, SLC2A1

Neuropathies **Prof. Bernd Rautenstrauss, ScD; Angela Abicht, MD

Multi-Gene Panel: Hereditary Neuropathies Detailed information available at www.mgz-muenchen.de

Hereditary Neuropathy with Pressure Palsy, HNPP PMP22 Deletion PMP22 Point mutation

Hereditary Motor and Sensory Neuropathy HMSN1, CMT1A PMP22 Duplication

HMSN1, predominantly demyelinating PMP22 Cx32 PRPS1 MPZ SH3TC2 SIMPLE EGR2 PRX HYCCIN (with cataracts) NDRG1 FGD4 MTMR2 SBF2 (with glaucoma) FIG4 Congenital Cataract Facial Dysmorphism Neuropathy Syndrome, CCFDN, CTDP1

HMSN2, predominantly axonal MFN2 LMNA RAB7 TRPV4 NEFL AARS GDAP1 BSCL2 (Exon 3) HSPB1 HSPB8 MED25 (Mutation A335V)

HMSN, intermediary: DNM2 YARS KARS Distal Hereditary Motor Neuropathies (dHMN)

HSPB8 HSPB1 HSPB3 GARS SETX DCTN1 (ALS-associated)

Giant Axon Neuropathy, GAN1, GAN Hereditary Sensory and Autonomic Neuropathies

HSAN1A, SPTLC1 HSAN1C, SPTLC2 HSAN2, WNK1 HSAN4, NTRK1 HSAN5, NGFB HSAN2C, KIF1A

Hereditary Neuralgic Amyotrophy, HNA, SEPT9 Erythermalgia, SCN9A Pain Tolerance, SCN9A Andermann Syndrome, ACCPN, KCC3, SLC12A6

Familial Ophthalmological DiseasesTeresa Neuhann, MD; Prof. Bernd Rautenstrauss, ScD

Hereditary Optic Atrophies Autosomal dominant Optic Atrophy OPA1 OPA3 Leber's Hereditary Optic Neuropathy, LHON, ND1, ND4, ND6 Autosomal recessive Optic Atrophy, TMEM126

X-Linked Congenital Nystagmus, FRMD7 Isolated Ectopia lentis ADAMTSL4 FBN1 LTBP2 Syndromic Ectopia lentis

Weill-Marchesani Syndrome ADAMTS10 ADAMTS17 Marfan Syndrome, FBN1

Aniridia, PAX6 Primary Congenital Glaucoma, CYP1B1 Keratoconus, VSX1 Stickler Syndrome COL2A1 COL11A1 Microphthalmia / Anophthalmia, SOX2, OTX2

Congenital Myasthenic Syndromes (CMS) /Fetal Akinesia Sequence **Angela Abicht, MD

Multi-Gene Panel: Congenital Myasthenic Syndromes Detailed information available at www.mgz-muenchen.de

Congenital Myasthenic Syndromes / Fetal Akinesia GFPT1 CHRNE CHRNA1 CHRNB1 CHRND CHRNG RAPSN DOK7 COLQ CHAT SCN4A

Muscular DiseasesAngela Abicht, MD; Stefanie Bulst, PhD;Prof. Elke Holinski-Feder, MD

Centronuclear Myopathy MTM1 DMN2 RYR1 BIN1 Congenital Muscular Dystrophy, CMD

COL6A1 COL6A2 COL6A3 CHKB

LMNA LAMA2 FKRP SEPN1 Congenital Myopathy

Core Myopathy RYR1 SEPN1 Nemaline Myopathy ACTA1 CFL2 NEB

TPM2 TPM3 TNNT1 KBTBD13

Limb-Girdle Muscular Dystrophy CAV3 FKRP LMNA

Malignant Hyperthermia RYR1 CACNA1S (p.R1086H) Duchenne / Becker Muscular Dystrophy, DMD

Deletions / duplications in all 79 exons Point mutations Linkage analysis

Emery-Dreifuss Muscular Dystrophy LMNA EMD Myoadenylate Deaminase Deficiency, MAD, AMPD1 Myotonic Dystrophy Type 1, DMPK Myotonic Dystrophy Type 2, PROMM, ZNF9 Myopathy with Neutral Lipid Storage Disease

CPT2 ETFDH PNPLA2 Myotonia congenita, CLCN1 Paramyotonia congenita, SCN4A Myotonia, CAV3-associated

Neurodegenerative Diseases / AtaxiaAngela Abicht, MD; Prof. Bernd Rautenstrauss, ScD

Amyotrophic Lateral Sclerosis, ALS SOD1 C9ORF72 TARDBP FUS FIG4 ANG

Apolipoprotein E4 Allele with Alzheimer's Disease, APOE Ataxia with Oculomotor Apraxia

APTX (AOA1) SETX (AOA2) Ataxia Telangiectasia, ATM Chorea Acanthocytosis, VPS13A Dementia, frontotemporal and / or ALS, C9ORF72 Dementia, familial, Alzheimer type PSEN1 PSEN2 APP Dentatorubral-Pallidoluysian Atrophy, DRPLA, ATN1 Fragile X-associated Tremor / Ataxia Syndrome, FXTAS, FMR1 Friedreich's Ataxia, FRDA Huntington's Disease, HTT Spinal Muscular Atrophy, Type I, II, III, SMN1 Spinal Muscular Atrophy with Respiratory Distress, IGHMBP2 Spinal Muscular Atrophy, X-linked, infantile, SMAX2, UBE1 Spinal and Bulbar Muscular Atrophy, Kennedy Type, AR Spinocerebellar Ataxia Types 1, 2, 3, 6, ATXN1, 2, 3, CACNA1A Spinocerebellar Ataxia Type 7, ATXN7 Spinocerebellar Ataxia Type 8, ATXN8 Spinocerebellar Ataxia 17, TBP

Epilepsies **Angela Abicht, MD; Prof. Bernd Rautenstrauss, ScD; Prof. Elke Holinski-Feder, MD

Multi-Gene Panel: Epileptic Encephalopathy Detailed information available at www.mgz-muenchen.de

Infantile Epilepsy SCN1A, Dravet Syndrome PCDH19, with mental retardation (girls only) CDKL5 (predominantly girls) FOXG1 ARX, X-linked West Syndrome STXBP1, Ohtahara Syndrome SLC2A1, GLUT1 Deficiency Syndrome

Early Infantile Epilepsy with suspected syndrome SLC9A6, X-linked mental retardation Christianson type MECP2, Rett Syndrome Angelman Syndrome, methylation test, UBE3A

GLUT1 Deficiency Syndrome, GLUT1, SLC2A1 GEFS+ (Generalized Epilepsy with Febrile Seizures plus)

SCN1A SCN1B SCN2A GABRD (Juvenile Myoclonic Epilepsy) GABRG2 (Absence Epilepsy in Childhood)

Benign Familial Neonatal Convulsions (BFNC) KCNQ2 KCNQ3

Sample: EDTA blood HEPARIN blood Other ! IMPORTANT : EDTA blood of parents required Diagnostics only upon prior arrangement

Patient's name:

Mitochondrial DiseasesRita Horváth, MD; Angela Abicht, MD; Birgit Czermin, PhD

Multi-Gene Panel: Mitochondrial Diseases Detailed information available at www.mgz-muenchen.de

Select according to clinical symptoms: Coenzyme Q10 Deficiencies:

PDSS1 PDSS2 ETFDH ETFA/B COQ2 COQ6 COQ9 APTX CABC1 / ADCK3

Congenital Muscular Dystrophy w/ enlarged Mitochondria, CHKB Early Infantile (Hepatic) Encephalomyopathy

POLG (Alpers Syndrome) PEO1 (Twinkle) DGUOK MPV17 hepatic form TK2 RRM2B myopathic form SUCLA2 SUCLG1 encephalomyopathic form

Kearns-Sayre Syndrome / CPEO sporadic, mtDNA deletions in muscle DNA familial POLG PEO1 (Twinkle) TK2 ANT1 POLG2 RRM2B OPA1

Leigh / Leigh-like Syndrome MTATP6+8 PDHA1 SURF1 COX6B1 FASTKD2

MELAS mt-tRNALeu (m.3243A>G) mt-tRNAs MERRF mt-tRNALys (m.8344A>G) mt-tRNAs Mitochondrial Cardiomyopathy

TAZ / Barth SCO2 mt-tRNAs MTATP6+8 SLC25A3 TMEM70 COX15 SDHA AGK

Mitochondriale Myopathy CHKB mtDNA deletions / point mutations in muscle DNA Complete sequencing of mtDNA

MNGIE / Mitochondrial Neurogastrointestinal Encephalomyopathy: ECGF1 / TYMP

Mitochondrial Translation Deficiency mt-tRNAs TSFM EFG1 / GFM1 PUS1 TUFM MRPS16 TRMU YARS2

Multiple Acyl-CoA Dehydrogenase Deficiency ETFA ETFB ETFDH ACADVL

NARP / Neuropathy, Ataxia, and Retinitis pigmentosa, MTATP6+8 Optic Atrophy

LHON / Leber's Hereditary Optic Neuropathy m.3460G>A (ND1) m.11778G>A (ND4) m.14484T>C (ND6) MTND1-6 Autosomal dominant Optic Atrophy, ADOA, OPA1

Pearson Syndrome: mtDNA deletion Rhabdomyolysis, Exercise Intolerance, Elevated CK

CPT2 LPIN1 ETFDH MTCYB ACADVL SANDO / Sensory Ataxia, Neuropathy, Dysarthria, Ophthalmoplegia

POLG PEO1 (Twinkle) Thiamine-Responsive Megaloblastic Anemia, TRMA, SLC19A2 Wolfram Syndrome, DIDMOAD, WFS1

Select according to biochemical test results (muscle biopsy): Complex I Deficiency: NDUFA1 NDUFA8 NDUFA11

NDUFS1 NDUFS2 NDUFS3 NDUFS4 NDUFS6 NDUFS7 NDUFS8 NDUFV1 NDUFV2 ACAD9

Complex II Deficiency: SDHA SDHAF1 Complex III Deficiency: BCS1L MTCYB TTC19 Complex IV Deficiency: MTCOI-III SCO1

SCO2 SURF1 COX10 COX15 TACO1 ETHE1 COX6B1 FASTKD2

Complex V Deficiency: MTATP6+8 TMEM70 mtDNA Depletions: POLG PEO1 (Twinkle) AGK

DGUOK MPV17 TK2 RRM2B SUCLA2 SUCLG1

Translation Deficiency: TSFM mt-tRNAs EFG1 / GFM1 TUFM MRPS16 TRMU PUS1 YARS2 EARS2 AARS2 MTO1 MTFMT

Normal Activity: mtDNA Deletionen POLG ANT1 POLG2 RRM2B OPA1 PEO1/Twinkle SLC25A3 (mt phosphate carrier)

Coenzyme Q10 Deficiency: See genes listed above.

mtDNA targeted diagnostics: MTCOI-III MTCYTB MTATP6+8 MTND1-6 mt-tRNAs Analysis of mtDNA deletions Analysis of mtDNA depletion Complete sequencing of mtDNA

Vascular DiseasesAngela Abicht, MD; Teresa Neuhann, MD

Porencephaly / Cerebral Microangiopathy / Apoplexy COL4A1 COL4A2

Marfan Syndrome, FBN1

Familial Metabolic DiseasesStephanie Kleinle, PhD

Alpha 1-Antitrypsine Deficiency, PI1 Apolipoprotein B100, ABOB Apolipoprotein E, APOE Beta Oxidation Defects

ETFA ETFB ETFDH ACADVL Congential Adrenal Hyperplasia, CAH, CYP21A2 Creatine Transporter Deficiency, SLC6A8 Cystic Fibrosis, CFTR (please indicate ethnic origin)

Screening for the most common mutations

Deletion / duplication in all CFTR exons Complete analysis of the CFTR gene Mutation F508del

Gilbert's Syndrome (Gilbert-Meulengracht), UGT1A1 GLUT1 Deficiency Syndrome, GLUT1, SLC2A1 Hemochromatosis, HFE Menkes Syndrome, ATP7A

Infertility and Reproductive Medical GeneticsUlrike Schön, PhD; Udo Koehler, PhD

Azoospermia Factor, AZF CBAVD (Congenital Bilateral Aplasia of Vas deferens) / 5T-Allel Polar Body / Preimplantation Diagnostics (PGD)

Monogenic diseases Array-CGH

Premature Ovarian Failure, POF, FMR1 Sex-determining Region Y, SRY (deletion analysis)

Parentage / Linkage / Human Leukocyte AntigenAndreas Laner, PhD

DNA asservation Contamination test HLA-DQB1*0602 in cases of narcolepsy Linkage analysis (upon prior arrangement) Paternity / Maternity / Familial relationship testing Uniparental Disomy 2, 7, 9, 11, 13, 14, 15, 16, 20, 22 X-Inactivation

PharmacogeneticsAndreas Laner, PhD

5FU toxicity, DPD Thiopurine toxicity, TPMT Irinotecan toxicity, UGT1A1 MTX toxicity, MTHFR CYP2D6 in cases of Tamoxifen therapy

Thrombophilia/ Hematology Beta Thalassemia, HBB Factor V Leiden mutation, F5 Methylenetetrahydrofolate reductase mutation, MTHFR Prothrombin gene mutation, F2 Sickle-cell anemia, HBB X-Linked Agammaglobulinemia (Bruton type), BTK

!

In order to select the appropriate gene(s), please refer to the anamnesis forms and/or information on our website: www.mgz-muenchen.de / downloads.html **Our lab is accredited by the German National Accreditation Council (DAkkS) in accordance with DIN EN ISO/IEC 15189 and DIN EN ISO 17025 — except for those analyses marked with an asterisk (*).

Sample: EDTA blood HEPARIN blood Other ! IMPORTANT : EDTA blood of parents required Diagnostics only upon prior arrangement