# Presentation: 205713

## Molecular Diagnostics at 

**The Hospital for Sick Children**

**Dr. Peter Ray**
**www.sickkids.ca/Molecular**

## Slide 2

## Molecular Diagnostic Laboratory

** ****Opened in 1987 (DMD, CF)**
** ****currently 15000 specimens per year**
** ****expanding 20% per year**
** ****12 Technologists**
** ****30 tests **
** ****diagnosis, carrier testing, PND**

## Molecular Diagnostic Laboratory

**HHT**
**Hypochondroplasia**
**Pfeiffer syndrome**
**Prader-Willi syndrome**
**Retinoblastoma**
**Saethre-Chotzen syndrome**
**Schwachman-Diamond Syndrome**
**Spinal and bulbar muscular atrophy**
**Spinal Muscular Atrophy**
**Tay-Sachs disease**
**Thanatophoric Dysplasia (Type I & II)**
**Bone Marrow Transplant Testing**
**DNA extraction/banking**
**Identity testing**
**X-inactivation**
**Y-specific marker (ZFX/ZFY)**
**Zygosity Testing**

**Achrondroplasia**
**Angelman Syndrome**
**Apert Syndrome**
**Batten Disease (NCL)**
**Beckwith-Wiedemann syndrome**
**Canavan disease**
**Craniosynostosis, non-syndromic**
**Crouzon/Jackson-Weiss syndrome**
**Cystic Fibrosis****	****	**
**Duchenne/Becker Muscular Dystrophy**
**Fabry disease**
**Familial Dysautonomia****	**
**Fragile X syndrome**
**FRAXE**
**Gaucher disease**
**Hearing loss, non syndromic**
**Hunters disease**

## Types of Mutations Tested

**Types of Mutations Tested**

**Disease**

- Point mutations?

- Deletions &
- duplications?

- Few recurrent
- mutations?

- Many unique
- mutations?

- Also with point
- mutations?

- Whole gene?
- Some exons?

- Other mutations?

## Diagnosis of Batten Disease

**Diagnosis of Batten Disease**

**Neuronal Ceroid Lipofuscinoses**

## Primer Extension Test for NCL Mutations

**Normal**

**Mutant**
**C451T**

**Primer Extension Test for NCL Mutations**

## Multiplexed Analysis of 9 NCL Mutations

**Normal**

**C70G**

**IVS**

**delAT**

**1.02del**

**C622T**

**C451T**

**A223C**

**A364T**

**G284V**

**Multiplexed Analysis of 9 NCL Mutations**

## Duchenne Muscular Dystrophy

**Duchenne Muscular Dystrophy**

## DMD Mutation Types

**DMD Mutation Types**

## Deletions in DMD Gene

**3'**

**5'**

**Deletions in DMD Gene**

**Exons**

**BMD**

**DMD**

**Intermediate**

## DMD Deletion Carrier Analysis

**DMD Deletion Carrier Analysis**

## DMD Deletion/Duplication Analysis – 79 exons

**5, 15, 25, 32, 43, 52, 63, 73**

**BP, 6, 17, 26, 33, 45, 55, 65, 75**

**10, 18, 27, 35, 44, 56, 66, 76**

**9, 19, 28, 36, 48, 57, 68, 77**

**8, 20, 29, 39, 49, 59, 69, 79**

**DMD Deletion/Duplication Analysis – 79 exons**

**exon**

## DMD Mutation Types

**DMD Mutation Types**

## DNA Sequencing

## Automated Mutation Detection

**Automated Mutation Detection**

**ABI SeqScape**

## Slide 17

## Interpretive Information Sheet

**Interpretive Information Sheet**

## Molecular Genetic Testing

**www.ncbi. nlm.nih.gov**
**www.genetests.org**

**Molecular Genetic Testing**

## HSC - DNA Clearing House

**Resource Centre for Hospital Physicians**
**Genetic Counsellor and Lab  Technologists**
**Advise on what testing is available and where**
**Extract DNA and send out samples**
**Track reports**
**Assist with interpretation and patient counseling**

## Molecular Diagnostics at 

**The Hospital for Sick Children**

**Dr. Peter Ray**
**www.sickkids.ca/Molecular**