TY - JOUR
T1 - Characterization of a COLIAI splicing defect in a case of Ehlers-Danlos syndrome type VII
T2 - Further evidence of molecular homogeneity
AU - D'Alessio, Marina
AU - Ramirez, Francesco
AU - Blumberg, Bruce D.
AU - Wirtz, Mary K.
AU - Rao, Validi H.
AU - Godfrey, Maurice D.
AU - Hollister, David W.
PY - 1991/8
Y1 - 1991/8
N2 - A child affected by the type VII form of Ehlers-Danlos syndrome (EDS VII) was shown to have a heterozygous structural defect in the amino-terminus of pro-α1(I) collagen. As a result, type I procollagen trimers containing defective subunits are not converted to mature collagen molecules. To identify the cause of the protein abnormality, specifically primed cDNAs and genomic DNA were PCR amplified and sequenced. This analysis disclosed that the protein structural defect is caused by a single base substitution (A for G) at position - 1 of the splice donor site of intron 6 of the pro-α1(I) collagen gene (COL1A1). The affected allele produces (a) transcripts lacking exon 6 sequences and (b), in lesser amount, normally spliced transcripts. Furthermore, the rate of exon 6 skipping is temperature dependent, for it appears to decrease substantially when the patient's fibroblasts are incubated at 31°C. These findings are similar to those we previously reported for other unrelated EDS VII cases and, therefore, reemphasize the molecular homogeneity of this rare connective tissue disorder.
AB - A child affected by the type VII form of Ehlers-Danlos syndrome (EDS VII) was shown to have a heterozygous structural defect in the amino-terminus of pro-α1(I) collagen. As a result, type I procollagen trimers containing defective subunits are not converted to mature collagen molecules. To identify the cause of the protein abnormality, specifically primed cDNAs and genomic DNA were PCR amplified and sequenced. This analysis disclosed that the protein structural defect is caused by a single base substitution (A for G) at position - 1 of the splice donor site of intron 6 of the pro-α1(I) collagen gene (COL1A1). The affected allele produces (a) transcripts lacking exon 6 sequences and (b), in lesser amount, normally spliced transcripts. Furthermore, the rate of exon 6 skipping is temperature dependent, for it appears to decrease substantially when the patient's fibroblasts are incubated at 31°C. These findings are similar to those we previously reported for other unrelated EDS VII cases and, therefore, reemphasize the molecular homogeneity of this rare connective tissue disorder.
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M3 - Article
C2 - 1867198
AN - SCOPUS:0026323643
SN - 0002-9297
VL - 49
SP - 400
EP - 406
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 2
ER -