A protein truncation test for Emery-Dreifuss muscular dystrophy (EMD): detection of N-terminal truncating mutations.
X-linked Emery-Dreifuss muscular dystrophy (EMD) is caused by mutations in the emerin gene. Since the emerin gene is ubiquitously expressed and since all EMD mutations published so far should be detectable by an RNA-based mutation assay, we have designed a protein truncation test for emerin. To facilitate the detection of mutations in the translation initiation site, reported for several EMD-cases, the standard tailed forward PTT-primer had to be modified. The effectiveness of the assay was established by a mutation scan in four EMD-patients. Two patients could be shown to carry emerin mutations, one affecting the ATG translation initiation codon. The PTT-assay did not detect a mutation in the two other patients. Since an immunohistochemical analysis of patient-derived cells revealed normal emerin levels, these patients are thus affected by another muscular dystrophy, most likely autosomal dominant EMD.
de Koning Gans
P A
PA
MGC-Department of Human Genetics, Leiden University Medical Center, The Netherlands.
Ginjaar
I
I
Bakker
E
E
Yates
J R
JR
den Dunnen
J T
JT
D003062:Codon / Q000235:genetics; D004247:DNA / Q000235:genetics; D008040:Genetic Linkage; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics*; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics*; D009136:Muscular Dystrophies / Q000175:diagnosis* / Q000235:genetics*; D020389:Muscular Dystrophy, Emery-Dreifuss; D009154:Mutation / Q000502:physiology*; D009687:Nuclear Proteins; D014176:Protein Biosynthesis / Q000235:genetics; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013946:Thymopoietins / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D014960:X Chromosome
D003062:Codon; D008565:Membrane Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D013946:Thymopoietins; C092710:emerin; D012313:RNA; D004247:DNA