ABSTRACT
We report on a kindred segregating 2 distinct mutations of a dystrophin gene. DNA analysis showed that the second mutation, a deletion, arose in the same gene carrying the primary defect which produced a Becker phenotype in the affected males. The DNA data for this family are reported and the alternative explanations of chance occurrence and premutation are discussed to explain these unusual findings.
Subject(s)
Chromosome Deletion , Dystrophin/genetics , Muscular Dystrophies/genetics , Child , DNA/analysis , Fetal Diseases/genetics , Fluorescent Antibody Technique , Haplotypes , Humans , Male , Mutation/genetics , PedigreeABSTRACT
The majority of Duchenne and Becker muscular dystrophy cases are caused by deletions observable in Southern blots with cDNA probes for the gene. When the deletion includes polymorphic probes, they may be used to determine carrier status by deletion segregation analysis: non-inheritance of parental alleles, or heterozygosity. The polymorphic genomic probe P20 is deleted in a large percentage of probands. P20 hybridizes with two constant fragments of 6.7 and 0.8 kb in Taql digests. In a number of probands, only the larger P20 Taql fragment is deleted. This study demonstrates that this fragment corresponds with the polymorphic EcoRV and Mspl fragments of P20. Families in which the upper Taql fragment is deleted may be screened for carrier status using non-inheritance of parental alleles or heterozygosity of P20 in EcoRV or Mspl digests.
Subject(s)
Genetic Carrier Screening/methods , Muscular Dystrophies/diagnosis , Polymorphism, Genetic , Blotting, Southern , DNA Probes , Deoxyribonuclease HpaII , Deoxyribonucleases, Type II Site-Specific , Humans , In Vitro Techniques , Muscular Dystrophies/genetics , Polymorphism, Restriction Fragment LengthABSTRACT
This article describes the diagnostic algorithm being used for the management of the 148 families affected by Duchenne or Becker muscular dystrophy who are known to the Molecular Neurogenetics Laboratory in the Department of Neuropathology, Royal Perth Hospital. In 60 families from whom DNA has been obtained, 41 mutations (39 deletions and two duplications) of the Duchenne muscular dystrophy gene (DMD) have been identified by means of complementary DNA (cDNA) probes. DNA-based screening has clarified the carrier status of 45 at-risk women, and 13 pregnancies have been monitored. In addition, cDNA screening of all relevant patients with autosomal recessive muscular dystrophy, spinal muscular atrophy or limb-girdle muscular dystrophy facilitated the correct diagnosis of Becker muscular dystrophy in three patients.
Subject(s)
Genetic Carrier Screening/methods , Muscular Dystrophies/diagnosis , Prenatal Diagnosis/methods , Algorithms , Chromosome Deletion , DNA Probes , Female , Fetal Diseases/diagnosis , Fetal Diseases/genetics , Genetic Techniques , Humans , Male , Muscular Dystrophies/genetics , Pedigree , Polymorphism, Restriction Fragment Length , Pregnancy , Risk , X Chromosome/ultrastructureABSTRACT
A 31-year-old man previously investigated for a neuromuscular disorder was diagnosed as having either limb-girdle dystrophy, spinal muscular atrophy, or Becker muscular dystrophy. Extensive clinical and special neurological investigations failed to clarify this differential diagnosis. However, recent DNA studies have shown a deletion of the dystrophin gene, thereby providing an unequivocal diagnosis of Becker muscular dystrophy. The application of molecular genetic techniques in the diagnosis of inherited neuromuscular disorders is discussed.
