The role of muscle biopsy in analysis of the dystrophin gene in Duchenne muscular dystrophy: experience of a national referral centre.
Although the majority (65%) of boys with Duchenne muscular dystrophy (DMD) carry a deletion in the dystrophin gene, finding mutations in the remaining families is vital for counselling. We have provided a comprehensive mutation service as a national referral centre for France for over 10 years and we report here our experience. Mutation screening is on mRNA from a muscle biopsy. We have detected 79 mutations in 89 samples referred with a diagnosis of DMD, which is the most comprehensive survey to date of the full range of nondeletion mutations. Although some mutations were nonsense mutations, some frameshift mutations and some splicing mutations, all of them led to the generation of premature stop codons or a shortened product which could be detected using the Protein Truncation Test. We recommend a protocol which is robust and sensitive applied to the entire coding region reverse-transcribed from dystrophin transcripts from muscle biopsy.
Tuffery-Giraud
Sylvie
S
Laboratoire de Génétique Moleculaire et Chromosomique, Institut Universitaire de Recherche Clinique (IURC), CHU de Montpellier, 641 avenue du Doyen G. Giraud, 34093 Montpellier Cedex 5, France. tuffery@igh.cnrs.fr
Saquet
Céline
C
Chambert
Sylvie
S
Echenne
Bernard
B
Marie Cuisset
Jean
J
Rivier
François
F
Cossée
Mireille
M
Philippe
Christophe
C
Monnier
Nicole
N
Bieth
Eric
E
Recan
Dominique
D
Antoinette Voelckel
Marie
M
Perelman
Serge
S
Lambert
Jean-Claude
JC
Malcolm
Sue
S
Claustres
Mireille
M
D001706:Biopsy / Q000379:methods; D015139:Blotting, Southern; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods; D016189:Dystrophin / Q000235:genetics*; D005192:Family Health; D035082:Federal Government; D005602:France; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism / Q000473:pathology*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics*; D009154:Mutation; D012333:RNA, Messenger / Q000096:biosynthesis; D012017:Referral and Consultation / Q000706:statistics & numerical data*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D016189:Dystrophin; D012333:RNA, Messenger