DMPK Detection of Abnormal Alleles with Interpretation information

Sample Requirements:	Lavender (EDTA) top tube

Minimum Sample Volume:	2 mL per tube (Child) 3 mL per tube (Adult)

Ship to:	University of Iowa Hospitals and Clinics Department of Pathology Client Services, Rm 5231 RCP 200 Hawkins Drive Iowa City, IA 52242

Shipping Requirements:	Overnight delivery with hazardous material precautions Room temperature (DO NOT FREEZE) Delivery: Monday - Friday Samples may be stored at refrigerator temperature if shipment is delayed.

All information must be provided before testing is performed
Specimen Information:	Patient identifier (SSN if available) Patient full name (Last, First, MI) Date of birth and sex Date and time of collection Ordering physician Clinical information and family history Next of Kin (Name, address, phone number) Name of person or group providing genetic counseling

Billing Information:	Please see Billing Options

Reporting Information:	Because of confidentiality issues, the report will not be released to any other individual or institution than is listed on this form. Physician or institution to send report to Address to send report to Phone number of individual or institution above Fax number to send report to if desired

Turn Around Time:	21 days

CPT Codes:	81404

Background:	Type1 Myotonic dystrophy (DM1) is the most common form of adult onset muscular dystrophy with an incidence of approximately 1 in 8,000 in populations of European decent. The disease is characterized by myotonia, muscle wasting, progressive weakness, cataracts, frontal balding, and cardiac conduction defects. The phenotype associated with congenital DM includes hypotonia and mental retardation. DM is a dominant disorder that exhibits extremely variable penetrance and anticipation within families. The disease is almost always associated with an expansion of a CTG tandem repeat in the 3' untranslated region of the myotonic dystrophy protein kinase (DMPK) gene on chromosome 19q13.2-q13.3. Individuals with < 50 repeats are unaffected although, in rare instances, 35 to 49 repeat alleles have been shown to be unstable when passed from parent to child. Alleles with between 50 and 90 repeats fall within the minimal disease category often associated with late onset DM. Individuals with between 100 and 349 repeats typically exhibit classic adult onset. Juvenile onset is often associated with expansions of 350 to 750 repeats, and patients with the congenital form of DM normally have expansions >750 repeats which are inherited exclusively from the mother. It should be noted that the genotype-phenotype correlation is not precise enough to be used clinically. The number of CTG tandem repeats within the DMPK gene is routinely determined with PCR and Southern blot analyses of genomic DNA.

Selected References:	Brook, et al. (1992) Molecular Basis of Myotonic Dystrophy: Expansion of a Trinucleotide (CTG) Repeat at the 3' End of a Transcript Encoding a protein Kinase Family Member. Cell, Vol 68:798-808. Fu, et al. (1992) An Unstable Triplet Repeat in a gene Related to Myotonic Dystrophy. Science, Vol 255: 1256-1258. Mahadevan, et al. (1992) Myotonic Dystrophy Mutation: An Unstable CTG Repeat in the 3' Untranslated Region of the Gene. Science, Vol 255: 123-1255. OMIM reference #160900.

Contact Information:	UIDL Client Services Monday-Friday - 8:00 am-7:30 pm CST Saturday - 8:00 am-1:00 pm CST Phone - 866-844-2522 Fax - 319-384-7213 Technical Test Information Molecular Pathology Laboratory 319-384-9568

04/13