TY - JOUR
T1 - Identification of female carriers for Duchenne and Becker muscular dystrophies using a FISH-based approach
AU - Ligon, Azra H.
AU - Kashork, Catherine D.
AU - Richards, C. Sue
AU - Shaffer, Lisa G.
N1 - Funding Information:
We thank the families who participated in this study, the clinicians who collected and submitted specimens, and Jessica Wu, Aimee Spikes, and Kay Atkins for their expert FISH analyses (Baylor College of Medicine, Houston, TX). This study was supported in part by a grant from the Muscular Dystrophy Association (to LGS).
PY - 2000/4
Y1 - 2000/4
N2 - Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive neuromuscular diseases caused by dystrophin gene mutations. Deletions, or more rarely duplications, of single or multiple exons within the dystrophin gene can be detected by current molecular methods in approximately 65% of DMD patients. Mothers of affected males have a two-thirds chance of carrying a dystrophin mutation, whilst approximately one-third of affected males have de novo mutations. Currently, Southern blot analysis and multiplex PCR directed against exons in deletion hot spots are used to determine female carrier status. However, both of these assays depend on dosage assessment to accurately identify carriers since, in females, the normal X chromosome is also present. To obviate quantitation of gene dosage, we have developed exon-specific probes from the dystrophin gene and applied them to a screen for potential carrier females using fluorescence in situ hybridization (FISH). Cosmid clones, representing 16 exons, were identified and used in FISH analysis of DMD/BMD families. Our preliminary work has identified multiple, informative probes for several families with dystrophin deletions and has shown that a FISH-based assay can be an effective and direct method for establishing the DMD/BMD carrier status of females.
AB - Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive neuromuscular diseases caused by dystrophin gene mutations. Deletions, or more rarely duplications, of single or multiple exons within the dystrophin gene can be detected by current molecular methods in approximately 65% of DMD patients. Mothers of affected males have a two-thirds chance of carrying a dystrophin mutation, whilst approximately one-third of affected males have de novo mutations. Currently, Southern blot analysis and multiplex PCR directed against exons in deletion hot spots are used to determine female carrier status. However, both of these assays depend on dosage assessment to accurately identify carriers since, in females, the normal X chromosome is also present. To obviate quantitation of gene dosage, we have developed exon-specific probes from the dystrophin gene and applied them to a screen for potential carrier females using fluorescence in situ hybridization (FISH). Cosmid clones, representing 16 exons, were identified and used in FISH analysis of DMD/BMD families. Our preliminary work has identified multiple, informative probes for several families with dystrophin deletions and has shown that a FISH-based assay can be an effective and direct method for establishing the DMD/BMD carrier status of females.
KW - Becker muscular dystrophy
KW - Carrier detection
KW - Diagnostic testing
KW - Duchenne muscular dystrophy
KW - FISH
KW - Laboratory validation
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U2 - 10.1038/sj.ejhg.5200450
DO - 10.1038/sj.ejhg.5200450
M3 - Article
C2 - 10854113
AN - SCOPUS:0034110622
SN - 1018-4813
VL - 8
SP - 293
EP - 298
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 4
ER -