Ehlers-Danlos syndrome type IV: phenotypic consequences of a splicing mutation in one COL3A1 allele.

Abstract

The features of a child with Ehlers-Danlos syndrome type IV (EDS IV) resulting from a mutation in one COL3A1 allele were studied. The child was heterozygous for a G-to Atransition at the splice donor site of intron 41. It resulted in the splicing out of the exon 41 encoded sequence from al(III) mRNA and the deletion of 36 amino acids from glycine7" to lysine"l0 of the triple helical domain of al(III) chains of type III collagen. The amount of type III collagen in the dermis was only about 11% of normal. The child had the acrogeric form of EDS IV. He had the characteristic facies with a pinched nose, thin lips, and prominent eyes. These facial features, his aesthenic build, thin skin, prominent subcutaneous veins, and aged hands produced a 'cachectic' appearance. These features were evident in early childhood and worsened up to 12j years when he was last reviewed. Spontaneous bruising, bleeding from the large bowel, constipation, and delayed gastric emptying were other features. In cross section, the dermal collagen fibrils were round and measured 93-3±11-5nm in diameter which was not significantly different from control values of 102-5 ± 13-4 nm. The serum type III procollagen amino-terminal propeptide level of 25-5 ng/ml was within the normal age matched values of 15-5 ± 7-7 ng/ml despite the low production of type III collagen

Congenital erythropoietic porphyria: identification and expression of 10 mutations in the uroporphyrinogen III synthase gene.

“…The IVS2 +' lesion occurred at invariant position 1 of intron 2, a mutation that typically results in exon skipping (37). Analysis of the RT-PCR products from the IVS2+1/L4F patient by AvaII digestion (which would only cleave the normal sequence) did not digest any normally sized transcripts, indicating that all the transcripts encoded by the IVS2 ' allele were aberrant (Fig.…”

Intestinal Perforation in Ehlers‐Danlos Syndrome After Enema Treatment for Constipation

“…In a mailed questionnaire assessing gastrointestinal disorders and bowel habits in 613 people with Ehlers‐Danlos syndrome, 24.5% of the respondents (total 208) reported that they were usually or always constipated (11). Constipation (2,12‐14), obstipation (3), and fecal impaction (14) are frequently present in EDS syndrome. These symptoms usually appear in later childhood (15) and adolescence (2).…”

Dynamic interactions between cells and their extracellular matrix mediate embryonic development

“…In addition, the alignment and density of collagen are the primary determinants of the tensile strength of the ECM (Kjaer, 2004). The importance of collagen is highlighted by the fact that mutations in collagens type I, III, V, or type III procollagen can result in Ehlers-Danlos syndrome, which is characterized by skin laxity and joint hypermobility (Superti-Furga et al, 1989;Sillence et al, 1991;Nicholls et al, 1996;Toriello et al, 1996;De Paepe et al, 1997;Smith et al, 1997). Synthesized collagen scaffolds show great promise for tissue engineering and regeneration.…”