Journal article
Identification of a point mutation and germinal mosaicism in a duchenne muscular dystrophy family
Human Mutation, Vol.3(2), pp.133-140
1994
Abstract
Duchenne and Becker muscular dystrophies (DMD and BMD) are allelic X-linked disorders arising from mutations in the (2.4 Mb) dystrophin gene at Xp21. We have applied the reverse transcriptase-polymerase chain reaction (RT-PCR) to identify a larger than normal dystrophin mRNA from a male with Duchenne muscular dystrophy and his younger affected brother. The increased size of the dystrophin mRNA was due to a splice-site mutation at the exon 26:intron 26 junction where a T to G substitution prevented normal RNA processing. A cryptic splice-site, downstream of the mutation, was activated during processing, resulting in the inclusion of 117 bases of intron 26. This insertion introduced an in-frame stop codon into the mature dystrophin mRNA. An allele-specific test was developed to identify the mutation and was applied to this family. Interestingly, the mother of the two affected boys did not carry the mutation, as determined by allele-specific amplification and direct DNA sequence analysis, indicating gonadal mosaicism. Her eldest daughter, designated as a carrier based upon conventional testing and haplotype analysis, also did not carry the family mutation. Initial haplotyping of the family appeared to be straightforward with gonadal mosaicism becoming evident only after allele-specific analysis. The application of linked markers to identify the disease allele for conventional genetic counselling would have been erroneous in this family and highlights the diagnostic power of precise identification of the disease-causing mutation.
Details
- Title
- Identification of a point mutation and germinal mosaicism in a duchenne muscular dystrophy family
- Authors/Creators
- S.D. Wilton (Author/Creator) - Queen Elizabeth II Medical CentreD.C. Chandler (Author/Creator) - Royal Perth HospitalB.A. Kakulas (Author/Creator) - Queen Elizabeth II Medical CentreN.G. Laing (Author/Creator) - Queen Elizabeth II Medical Centre
- Publication Details
- Human Mutation, Vol.3(2), pp.133-140
- Publisher
- John Wiley & Sons Inc.
- Identifiers
- 991005545409207891
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.255 Musculoskeletal Disorders
- 1.255.628 Duchenne Muscular Dystrophy
- Web Of Science research areas
- Genetics & Heredity
- ESI research areas
- Molecular Biology & Genetics