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Duchenne Muscular Dystrophy - ppt-2010213558
Duchenne Muscular Dystrophy - ppt-2010213558
Curtis Kendall
December 5, 2006
Duchenne Muscular
Dystrophy
Facts
DMD affects mostly males at a rate of 1 in 3,500
births.
There are over 200 types of mutations that can cause
any one of the forms of muscular dystrophy.
There are also mutations that occur within the same gene that
cause other disease types.
DMD is the most severe and common type of
muscular dystrophy.
DMD is characterized by the wasting away of muscles.
DMD is the most aggressive form of muscular
dystrophy.
Diagnosis in boys usually occurs between 16 months
and 8 years.
Parents are usually the first to notice problem.
Death from DMD usually occurs by age of 30.
Clinical Features
Genotype of DMD
Females carry the DMD gene on the X
chromosome.
Females are carriers and have a 50%
chance of transmitting the disease
in each pregnancy.
Sons who inherit the mutation will
have the disease.
Daughters that inherit the mutation
will be carriers.
The DMD gene is located on the Xp 21
band of the X chromosome.
Mutations which affect the DMD gene.
96% are frameshift mutations
30% are new mutations
10-20% of new mutations occur in
the gametocyte (sex cell, will be
pass on to the next generation).
The most common mutation are
repeats of the CAG nucleotides.
Genotype of DMD
(Cont.)
During the translocation process, a
mutation occurs.
Mutations leading to the absence of dystrophin
Very Large Deletions (lead to absence of dystrophin)
Mutations causing reading errors (causes a
degraded, low functioning DMD protein
molecule)
Stop mutation
Splicing mutation
Duplication
Deletion
Point Mutations
Clinical Features
Phenotype of DMD
Delays in early childhood stages involving muscle use, in 42% of
patients.
Delays in standing alone
Delays in sitting without aid
Delays in walking (12 to 24 months)
Toe walking or flat footednees.
Child has a hard time climbing.
Learning difficulties in 5% of patients.
Speech problems in 3% of patients.
Leg and calf pain.
Mental development is impaired. IQs usually below 75 points.
Memory problems
Carrying out daily functions
Increase in bone fractures due to the decrease in bone density.
Increase in serum CK (creatine phosphokinase) levels up to 10
times normal amounts.
Wheelchair bound by 12 years of age.
Cardiomyopathy at 14 to 18 years.
Few patients live beyond 30 years of age.
Reparatory problems and cardiomyopathy leading to congestive heart
failure are the usual cause of death.
Molecular Makeup
Becker Muscular Deletion or Duplication Creates A Protein That Same As But Less
Dystrophy That Change In-Frame Is Partially Functional Sever Then DMD But
Exons Onset At Greater Then
7 Years Old
DMD Related Dilated Effects The Cardiac No Dystrophin Tachycardia (Fat Heart
Cardiomyopathy Muscle Promoter and Transcriptions Being Beat) Leads To
The First Exon Carried Out In Cardiac Congestive Hear
Muscle Failure
Spinal Muscular Mutation In The SMN Degeneration of Motor Poor Muscle Tone,
Atrophy Gene Neurons Which Are Absence of Deep
Nerve Cells In The Tendon Reflexes
Spinal Cord.
3D Images of The Actin
Binding Sight Of Dystrophin
Bibliography
OMIM
MUSCULAR DYSTROPHY, DUCHENNE TYPE; DMD
#310200
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=310200
DYSTROPHIN; DMD
#300377
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?cmd=entry&id=300
377
Bookshelf
Genes and disease.
Bethesda (MD):
National Library of Medicine
Introduction to Genetic Analysis. 7th ed.
Griffiths, Anthony J.F.; Miller, Jeffrey H.; Suzuki, David T.; Lewontin,
Richard C.; Gelbart, William M.
New York: ; c1999.
Human Molecular Genetics 2 2nd ed.
Strachan, Tom and Read, Andrew P.
New York and London: ; c1999
GeneReviews
Editor-in-chief: Pagon, Roberta A. Associate editors: Cassidy, Suzanne
B.; Bird, Thomas C.; Dinulos, Mary Beth; Feldman, Gerald L.; Smith,
Richard J.H.; Dolan, Cynthia R. Technical editor: Baskin, Patricia K.
Seattle (WA): University of Washington; 1993-2006
Bibliography (Cont.)
PubMed
Houben F, Ramaekers FC, Snoeckx LH, Broers JL.
Role of nuclear lamina-cytoskeleton interactions in the maintenance of cellular
strength.
Biochim Biophys Acta. 2006 Sep 19;
Maeda M, Nakao S, Miyazato H, Setoguchi M, Arima S, Higuchi I, Osame M, Taira A,
Nomoto K, Toda H.
Cardiac dystrophin abnormalities in Becker muscular dystrophy assessed by
endomyocardial biopsy.
Am Heart J. 1995 Apr;
Kanagawa M, Toda T.
The genetic and molecular basis of muscular dystrophy: roles of cell-matrix linkage in
the pathogenesis.
J Hum Genet. 2006 Sep 13;
Beroud C, Tuffery-Giraud S, Matsuo M, Hamroun D, Humbertclaude V, Monnier N,
Moizard MP, Voelckel MA, Calemard LM, Boisseau P, Blayau M, Philippe C, Cossee M,
Pages M, Rivier F, Danos O, Garcia L, Claustres M
Multiexon skipping leading to an artificial DMD protein lacking amino acids from exon
45 through 55 could rescue up to 63% of patients with Duchenne muscular dystrophy.
Hum Mutat. 2006 Oct 13;
Ervasti JM.
Dystrophin, its interactions with other proteins, and implications for muscular
dystrophy.
Biochim Biophys Acta. 2006 Jun 7;