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Molecular mechanisms of classical Ehlers-Danlos syndrome (EDS).

ABSTRACT: Classical Ehlers-Danlos syndrome (EDS) is a heritable disorder characterized by joint hypermobility, skin hyperextensibility, and abnormal wound healing. The majority of affected individuals have alterations in 1 of the 2 type V collagen genes, COL5A1 and COL5A2. The most common mechanism is COL5A1 haploinsufficiency due to instability of the transcript of one allele. In dermal fibroblasts from our population of 76 individuals with clinical features of classical EDS, there were 21 (29.5%) with decreased expression of one COL5A1 allele, consistent with published estimates of the frequency of null alleles. We identified the causative mutation in nine of these cell strains (mutations for seven others had been previously described), and found two nonsense mutations, five splice mutations, and two insertion/deletions. The same type of genomic change at splice sites can have different effects at the RNA level and the outcome could not be predicted from the primary genomic DNA alteration.

SUBMITTER: Mitchell AL

PROVIDER: S-EPMC3827857 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Molecular mechanisms of classical Ehlers-Danlos syndrome (EDS).

Mitchell Anna L AL Schwarze Ulrike U Jennings Jessica F JF Byers Peter H PH

Human mutation 20090601 6

Classical Ehlers-Danlos syndrome (EDS) is a heritable disorder characterized by joint hypermobility, skin hyperextensibility, and abnormal wound healing. The majority of affected individuals have alterations in 1 of the 2 type V collagen genes, COL5A1 and COL5A2. The most common mechanism is COL5A1 haploinsufficiency due to instability of the transcript of one allele. In dermal fibroblasts from our population of 76 individuals with clinical features of classical EDS, there were 21 (29.5%) with d ...[more]

PMID: 19370768

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Project description:Ehlers-Danlos syndrome type IV, the vascular type of Ehlers-Danlos syndromes (EDS), is an inherited connective tissue disorder defined by characteristic facial features (acrogeria) in most patients, translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial, digestive and uterine complications, which are rarely, if at all, observed in the other forms of EDS. The estimated prevalence for all EDS varies between 1/10,000 and 1/25,000, EDS type IV representing approximately 5 to 10% of cases. The vascular complications may affect all anatomical areas, with a tendency toward arteries of large and medium diameter. Dissections of the vertebral arteries and the carotids in their extra- and intra-cranial segments (carotid-cavernous fistulae) are typical. There is a high risk of recurrent colonic perforations. Pregnancy increases the likelihood of a uterine or vascular rupture. EDS type IV is inherited as an autosomal dominant trait that is caused by mutations in the COL3A1 gene coding for type III procollagen. Diagnosis is based on clinical signs, non-invasive imaging, and the identification of a mutation of the COL3A1 gene. In childhood, coagulation disorders and Silverman's syndrome are the main differential diagnoses; in adulthood, the differential diagnosis includes other Ehlers-Danlos syndromes, Marfan syndrome and Loeys-Dietz syndrome. Prenatal diagnosis can be considered in families where the mutation is known. Choriocentesis or amniocentesis, however, may entail risk for the pregnant woman. In the absence of specific treatment for EDS type IV, medical intervention should be focused on symptomatic treatment and prophylactic measures. Arterial, digestive or uterine complications require immediate hospitalisation, observation in an intensive care unit. Invasive imaging techniques are contraindicated. Conservative approach is usually recommended when caring for a vascular complication in a patient suffering from EDS type IV. Surgery may, however, be required urgently to treat potentially fatal complications.

Dataset Information

Molecular mechanisms of classical Ehlers-Danlos syndrome (EDS).

Publications

Molecular mechanisms of classical Ehlers-Danlos syndrome (EDS).

Similar Datasets

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