A cysteine 3340 substitution in the dystroglycan-binding domain of dystrophin associated with Duchenne muscular dystrophy, mental retardation and absence of the ERG b-wave.

We report the first C-terminal missense mutation in a Duchenne muscular dystrophy patient. A G10227A transition of the dystrophin gene was found which resulted in the substitution of a highly conserved cysteine at position 3340 within the second half of the dystroglycan-binding domain. Residual amounts of 427 kDa dystrophin were detected in western blot analysis of the patient's muscle tissue, and immunohistological examination revealed weak traces of dystrophin on all fibers. Sarcolemmal staining intensity of 43 kDa beta-dystroglycan was also reduced. Mental retardation in our patient and absence of the b-wave in his electroretinogram indicate that central nervous functions of dystrophin isoforms also depend on the presence of cysteine 3340.

[1]  K. Campbell,et al.  Identification and Characterization of the Dystrophin Anchoring Site on β-Dystroglycan (*) , 1995, The Journal of Biological Chemistry.

[2]  S. Noguchi,et al.  Dystrophin-associated proteins in muscular dystrophy. , 1995, Human molecular genetics.

[3]  P. Ray,et al.  A novel dystrophin isoform is required for normal retinal electrophysiology. , 1995, Human molecular genetics.

[4]  L. Kunkel,et al.  Dp140: a novel 140 kDa CNS transcript from the dystrophin locus. , 1995, Human molecular genetics.

[5]  E. Ozawa,et al.  Mammalian alpha 1- and beta 1-syntrophin bind to the alternative splice- prone region of the dystrophin COOH terminus , 1995, The Journal of cell biology.

[6]  K. Davies,et al.  Increasing complexity of the dystrophin-associated protein complex. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[7]  G. Danieli,et al.  A possible missense mutation detected in the dystrophin gene by double strand conformation analysis (DSCA) , 1994, Neuromuscular Disorders.

[8]  J. Mendell,et al.  Identification of a missense mutation, single base deletion and a polymorphism in the dystrophin exon 16. , 1994, Human molecular genetics.

[9]  Kensuke Hayashi,et al.  Molecular organization at the glycoprotein-complex-binding site of dystrophin. Three dystrophin-associated proteins bind directly to the carboxy-terminal portion of dystrophin. , 1994, European journal of biochemistry.

[10]  M Bobrow,et al.  Searching for the 1 in 2,400,000: A review of dystrophin gene point mutations , 1994, Human mutation.

[11]  H. Thiele,et al.  Point mutations at the carboxy terminus of the human dystrophin gene: implications for an association with mental retardation in DMD patients. , 1993, Human molecular genetics.

[12]  I. Grunewald,et al.  Non-isotopic analysis of single strand conformation polymorphism (SSCP) in the exon 13 region of the human dystrophin gene. , 1993, Journal of medical genetics.

[13]  J. Ervasti,et al.  A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin , 1993, The Journal of cell biology.

[14]  J. Mendell,et al.  A missense mutation in the dystrophin gene in a Duchenne muscular dystrophy patient , 1993, Nature Genetics.

[15]  H. Lutz,et al.  A tightly membrane-associated subpopulation of spectrin is 3H-palmitoylated. , 1993, The Journal of biological chemistry.

[16]  L. Kunkel,et al.  The structural and functional diversity of dystrophin , 1993, Nature Genetics.

[17]  Hideko Yamamoto,et al.  Glycoprotein‐binding site of dystrophin is confined to the cysteine‐rich domain and the first half of the carboxy‐terminal domain , 1992, FEBS letters.

[18]  C. Caskey,et al.  An intact cysteine-rich domain is required for dystrophin function. , 1992, The Journal of clinical investigation.

[19]  D. Bentley,et al.  Point mutations in the dystrophin gene. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[20]  A. Simpson,et al.  Sm25, a major schistosome tegumental glycoprotein, is dependent on palmitic acid for membrane attachment. , 1991, The EMBO journal.

[21]  C. Marshall,et al.  All ras proteins are polyisoprenylated but only some are palmitoylated , 1989, Cell.

[22]  R. Heilig,et al.  The chicken dystrophin cDNA: striking conservation of the C‐terminal coding and 3′ untranslated regions between man and chicken. , 1988, The EMBO journal.

[23]  M. Koenig,et al.  Complete cloning of the duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals , 1987, Cell.