| Myotonic dystrophy
type 1 (DM1), OMIN 160900 ) is a multisystemic,
neuromuscular disease with an estimated incidence of 1 in 8000
in the European and North American population2). It
is the most common form of muscular dystrophy affecting adults
and is associated with abnormalities of other organs including
heart, eyes, endocrine system, central and peripheral nervous
system, gastrointestinal organs, bone and skin2).
Prominent symptoms are progressive muscle weakness and wasting,
cataracts, defects in cardiac conduction, mental retardation,
hypersomnia, abnormal glucose response, diabetes, calcifying
epitheliomas, and in males, frontal balding and testicular
atrophy.
The disorder is
inherited in an autosomal dominant way. In 1992, expansion of a
trinucleotide (CTG) repeat in the 3’ untranslated region of
the myotonic dystrophy serine-threonine protein kinase (DMPK)
gene on chromosome 19q13,3 was identified as the molecular basis
of myotonic dystrophy type 13,4). The CTG repeat is a
polymorphic locus in the normal population where it has a stable
range of 5-37 repeats. In affected patients, the repeat number
is expanded to 50-1000 repeats in mildly affected patients and
to >1000 repeats in severely affected patients with neonatal
respiratory distress, hypotonia and mental retardation5).
DM1 shows genetic anticipation in which the disease
severity is proportional, and the age-of-onset is inversely
proportional to the size of the triplet extension6).
The repeat number tends to increase in successive generations
and is both meiotically and mitotically unstable7).
The screening of
the DMPK gene for expansion of the triplet repeat supports the
clinical diagnosis of myotonic dystrophy and enables detection
of carriers of mutant alleles among family members of
DM1-patients.
When suspecting
myotonic dystrophy type 1, we routinely amplify and determine
the size of the target exon 15 from the genomic DNA of the
patient. We usually provide results of the analysis of exon 15
within 2 days after receipt of the sample.
When an abnormal
extention of the CTG-repeat is found, we recommend analyzing the
DMPK genes of the patient's relatives to detect carrier of the
gene defect.
1) The International
Myotonic Dystrophy Consortium (IDMC), Neurology 54:1218-1221.
New nomenclature and DNA testing guidelines for myotonic
dystrophy type 1 (DM1).
2) Harper, P.S. (1989) Myotonic dystrophy, 2nd. edn.,
Saunders, Philadelphia.
3) Mahadevan et al. (1992) Science 255:1253-1255.
An unstable triplet repeat in a gene related to myotonic
muscular dystrophy.
4) Brook et al. (1992) Cell 68:799-808. Molecular
basis of myotonic dystrophy: expansion of a trinucleotide (CTG)
repeat at the 3’ end of a transcript encoding a protein kinase.
5) Miller et al. (2000) EMBO J. 19:4439-4448.
Recruitment of human muscleblind proteins to (CUG)n
expansions associated with myotonic dystrophy.
6) Ashizawa et al. (1992) Neurology 42:1877-1883.
Anticipation in myotonic dystropy. II. Relationships between
clinical findings and structure of the GCT repeat.
7) Khajavi et al. (2001) Hum. Mol. Genet. 10:855-863.
Mitotic drive of expanded CTG repeats in myotonic dystrophy
type 1 (DM1).
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The recommended source for
genomic DNA is EDTA-blood. A typical sample volume is 0.5
ml. Blood samples can be send to us at ambient temperature.
Other sources may also be considered for analysis (e.g. tissue
biopsies or paraffin embedded material). |
| Please
contact us for an estimate
for the analysis of the DMPK gene of your patient.
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The screening service for
myotonic dystrophy type 1 is available 7 days
a week.
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