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New variants in COL5A1 gene among Polish patients with Ehlers-Danlos syndrome: analysis of nine cases.

ABSTRACT: Introduction:The Ehlers-Danlos syndrome (EDS) is a non-inflammatory, heritable connective tissue disorder divided into 13 types according to the 2017 International Classification of the Ehlers-Danlos syndromes. One of the subtypes of EDS, classical (cEDS), is characterized by joint hypermobility, skin hyperextensibility and atrophic scars, which are major criteria of cEDS. Aim:In this study, the first in Central Eastern Europe, 44 patients were investigated. All of them were tested for COL5A1 mutations with direct DNA sequencing. Material and methods:The study group included 44 patients of Polish origin, all of whom fulfilled criteria for the classical type of Ehlers-Danlos syndrome. Direct sequencing of the COL5A1, COL5A2 and COL1A1 c.934C>T genes was performed for all of them. Evaluation of potential pathogenicity of detected missense mutation was conducted using SIFT (Sorting Intolerant from Tolerant), PolyPhen-2, AlignGVGD (Align Grantham Variance/Grantham Difference). The effect of the splice site mutations was predicted by Human Splicing Finder and NetGene2 tools. Results:Among all tested patients, nine mutations of COL5A1 gene were detected (8 missense mutations and 1 splice site). The alterations identified by us are new, hitherto not described in other reports. Evaluation of the mutations by in silico tools indicate their pathogenicity. Conclusions:Our study is the first COL5A1 gene molecular investigation conducted among cEDS patients from Central Eastern Europe. Besides new COL5A1 variant findings, we gained molecular confirmation of clinical diagnosis of cEDS. In some cases, specific and adequate evaluation and classification of EDS patients based only on clinical features, may be difficult.

SUBMITTER: Junkiert-Czarnecka A

PROVIDER: S-EPMC6409875 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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New variants in <i>COL5A1</i> gene among Polish patients with Ehlers-Danlos syndrome: analysis of nine cases.

Junkiert-Czarnecka Anna A Pilarska-Deltow Maria M Bąk Aneta A Heise Marta M Haus Olga O

Postepy dermatologii i alergologii 20190222 1

<h4>Introduction</h4>The Ehlers-Danlos syndrome (EDS) is a non-inflammatory, heritable connective tissue disorder divided into 13 types according to the 2017 International Classification of the Ehlers-Danlos syndromes. One of the subtypes of EDS, classical (cEDS), is characterized by joint hypermobility, skin hyperextensibility and atrophic scars, which are major criteria of cEDS.<h4>Aim</h4>In this study, the first in Central Eastern Europe, 44 patients were investigated. All of them were teste ...[more]

PMID: 30858776

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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

New variants in COL5A1 gene among Polish patients with Ehlers-Danlos syndrome: analysis of nine cases.

Publications

New variants in <i>COL5A1</i> gene among Polish patients with Ehlers-Danlos syndrome: analysis of nine cases.

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