Temperature-dependent expression of a collagen splicing defect in the fibroblasts of a patient with Ehlers-Danlos syndrome type VII.
In this article we report the characterization of the molecular lesion in a patient with Ehlers-Danlos syndrome Type VII and provide evidence that a de novo substitution of the last nucleotide of exon 6 in one allele of the pro-alpha 2(I) collagen gene produces normally spliced mRNA and transcripts from which exon 6 sequences have been outspliced as well. Unexpectedly, the expression of the alternative splicing was found to be temperature-dependent, for missplicing in cellula is effectively abolished at 31 degrees C and gradually increases to 100% at 39 degrees C. In contrast, in a similar patient harboring a substitution in the obligatory GT dinucleotide of the 5' splice site of intron 6, complete outsplicing of exon 6 sequences was found at all temperatures.
Weil
D
D
Department of Microbiology, Morse Institute of Molecular Genetics, State University of New York Health Science Center, Brooklyn 11203.
D'Alessio
M
M
Ramirez
F
F
Steinmann
B
B
Wirtz
M K
MK
Glanville
R W
RW
Hollister
D W
DW
D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003094:Collagen / Q000235:genetics* / Q000302:isolation & purification; D004247:DNA / Q000235:genetics; D004535:Ehlers-Danlos Syndrome / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D005784:Gene Amplification; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D015183:Restriction Mapping; D014158:Transcription, Genetic
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D003094:Collagen; D004247:DNA