A new COL3A1 mutation in Ehlers–Danlos syndrome type IV

Abstract

The vascular type of the Ehlers–Danlos syndrome (Ehlers–Danlos syndrome type IV, EDS IV; OMIM #130050) is a rare connective tissue disorder with autosomal dominant transmission caused by mutations in the COL3A1 gene resulting in increased fragility of connective tissue with arterial, intestinal, and uterine ruptures and premature death. We present a 28‐year‐old female who in addition to typical EDS IV symptoms had severe peripheral artery occlusive disease (PAOD) and subtotal stenosis of the abdominal aorta. COL3A1 sequencing resulted in detection of an as yet undescribed mutation in exon 36 at position 2465 leading to a nucleotide replacement (c.2465G>C; p.G822A). Ultrastructural analysis of a skin biopsy revealed abnormal morphology and distribution of dermal collagen fibres. We conclude that PAOD is a possible manifestation of EDS IV and that further research is required to define its true prevalence among patients with EDS IV and its molecular pathology including genotype–phenotype correlation.

Melatonin promotes Cashmere goat (Capra hircus) secondary hair follicle growth: a view from integrated analysis of long non-coding and coding RNAs

“…By comparison of lncRNAs and mRNAs profiles affected by melatonin exposure, we found that THBS2 and COL4A2 were two key molecules involved, both of which are key genes involved in collagen fibrillogenesis [45,46], and researches on murine models demonstrated that THBS -/-mice showed abnormal formation of collagen fibers and COL4A2 -/-mice also showed abnormal matrix deposition, these together further demonstrated that melatonin might regulate Cashmere goat secondary hair follicle growth via ECM receptors. Furthermore, protein-protein interaction assay demonstrated that THBS2, COL3A1, DCN and LUM were key nodes in the regulatory network, all these four genes are also vital for collagen fibrillogenesis in the skin, which are essential for skin homeostasis, as gene knock out mice model of these genes showed abnormal collagen fibrils morphology in the skin [46][47][48][49].…”

Neurovascular manifestations of connective-tissue diseases: A review

“…Histological analysis of the aortic walls of patients with EDS IV show a broadened intima with fibrosis, abundant cholesterol crystals, and derangement of elastic fibers. 14 Skin biopsies of EDS patients indicate collagen bundles that are thin and rare in the dermis and hypodermal septae. Under polarized light, such collagen bundles are less refringent than in normal skin.…”

Homonymous Hemianopia Secondary to A Long Fusiform Aneurysm of Posterior Cerebral Artery in A Patient with Connective Tissue Disease

“…It is hypothesized that the poor assembly of these type III collagen fibers in EDS IV results in the neurovascular manifestations of EDS IV. 8,9 The potential relationship between collagen deficiencies in EDS and cerebral aneurysms has long been hypothesized but never tested in a prospective screening study. In EDS patients, intracranial aneurysms can be saccular or fusiform and are typically located in the cavernous sinus.…”

“…According to some studies, abnormal connective tissue, particularly collagen, is the most common cause of fusiform aneurysms after vascular events and infections. 9,10 The most common collagen abnormalities are Ehlers-Danlos Syndrome type IV and neurofibromatosis type I. The clinical features of café-au-mark type I neurofibromatosis lit spot, a pigmented spot on the skin with a predilection for the arm or thigh area, are associated with skeletal abnormality and peripheral neural sheath tumor.…”