International Myotonic Dystrophy Organization

CTG trinucleotide repeat length and clinical expression in a family with myotonic dystrophy.

Author: Takahashi S , Miyamoto A , Oki J , Okuno A

Source  Brain Dev, 18(2): 127-30 0

Abstract:

Unstable expansion of the CTG repeats in the 3' untranslated region encoding a member of the protein

kinase family in the q13.3 band on chromosome 19 is a mutation specific for myotonic dystrophy. To examine

the correlation between clinical expression and CTG trinucleotide repeat length, we carried out Southern

blot analysis in a family with myotonic dystrophy. In this pedigree, the expanded CTG repeats were

transmitted maternally. The mother had three female children. The mother had about 200 CTG repeats, and

the number of repeats for each child was about 800, 1500 and 1600 in birth order. The mother and the

patient with 800 repeats were unaware of muscle weakness or myotonia. Symptoms were present from age 3

years in the patient with 1500 repeats and from birth in the one with 1600 repeats. Although the mother

menstruated regularly, the patients with 800 and 1500 repeats both menstruated irregularly, and the one with

1600 repeats has never menstruated. The age of onset and severity of the disease were correlated with the

size of the expanded repeats. Endocrinological studies revealed that the basal levels of the gonadotropins,

PRL and E2 were within normal range, and a pituitary response to LHRH was observed. These data suggest that

the amenorrhea and menstrual irregularities were caused by a suprahypophyseal dysfunction. When

expanded CTG repeats are transmitted maternally, abnormal products resulting from the metabolic

disturbance in the affected mother may harm the fetus in utero. A heterozygous fetus, who has more CTG

repeats, may be unable to metabolize the pathologic products sufficiently and therefore may become more

severely affected. This may explain the exclusive maternal transmission of congenital myotonic

dystrophy.

Unique Identifier:  96319199

MajorMeSH Heading  Muscular Dystrophies GE , Trinucleotide Repeats

MinorMeSH Heading

Adolescence, Adult, Blotting, Southern, Case Report, DNA Mutational Analysis, Dysmenorrhea BL GE, Female,

Human, Muscular Dystrophies BL PH, Pedigree, Polymorphism, Restriction Fragment Length, Sex Hormones BL,

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ISSN:

03877604

Country of Publication:

NETHERLANDS