Cardiac valvular Ehlers‐Danlos syndrome is a well‐defined condition due to recessive null variants in COL1A2

@article{Guarnieri2019CardiacVE,
  title={Cardiac valvular Ehlers‐Danlos syndrome is a well‐defined condition due to recessive null variants in COL1A2},
  author={Vito Guarnieri and Silvia Morlino and Giuseppe Di Stolfo and Sandra Mastroianno and Tommaso Mazza and Marco Castori},
  journal={American Journal of Medical Genetics Part A},
  year={2019},
  volume={179},
  pages={846 - 851}
}
Cardiac valvular Ehlers‐Danlos syndrome (EDS) is a rare EDS subtype, caused by specific recessive variants in the gene encoding pro‐α2‐chain of type I collagen (COL1A2). Cardiac valvular EDS is mainly characterized by generalized/peripheral joint hypermobility, moderate–severe cardiac valvular disease, skin hyperextensibility and other minor soft tissues features. Only five molecularly confirmed patients have been reported to date. Here, we describe two additional affected sisters, who share… 

Multisystemic manifestations in a cohort of 75 classical Ehlers-Danlos syndrome patients: natural history and nosological perspectives

This study confirms that cEDS is mainly characterized by cutaneous and articular involvement, though none of their hallmarks was represented in all cases and suggests a milder multisystemic involvement and a more favorable natural history compared to other EDS subtypes.

The Ehlers–Danlos syndromes

The epidemiology, mechanisms, diagnosis and treatment of these syndromes are discussed, with common features including joint hypermobility, soft and hyperextensible skin, abnormal wound healing and easy bruising.

Ehlers-Danlos syndromes and their manifestations in the visual system

In this review, this review comprehensively gather and discuss the ocular manifestations of EDS and its thirteen subtypes in the clinical setting.

Molecular mechanisms and clinical manifestations of rare genetic disorders associated with type I collagen.

The relationship between clinical manifestations and type I collagen - related rare genetic disorders and their possible molecular mechanisms for different mutations and disorders are reviewed.

Dermatologic manifestations of pediatric cardiovascular diseases: Skin as a reflection of the heart

This review will focus on diseases with cardiocutaneous pathology with hopes of raising clinician awareness of these associations to decrease morbidity and mortality, as several of these diseases often result in fatal outcomes.

Genetic Polymorphisms of MMP1, MMP9, COL1A1, and COL1A2 in Polish Patients with Thoracic Aortopathy

The results of this study did not support associations between MMP1, MMP9, COL1A1, andCOL1A2 genetic variants with the risk of thoracic artery disease in Polish patients, however, rs1799750 MMP 1 and rs3918242 M MP9 seem to be associated with the degree of aortic regurgitation.

Collagen (I) homotrimer does not cause bone fragility but potentiates the osteogenesis imperfecta (oim) mutant allele

It is concluded that the presence of heterotrimeric collagen–1 in oim heterozygotes alleviates the effect of the oim mutant allele but a genetic interaction between homotrimic collagen-1 and the oIM mutant allele leads to bone fragility.

Collagen (I) homotrimer potentiates the osteogenesis imperfecta (oim) mutant allele and reduces survival in male mice

It is comprehensively shown for the first time that mice lacking the α2(I) chain do not have impaired bone biomechanical or structural properties, unlike oim homozygous mice, and a genetic interaction between homotrimeric collagen-1 and the oim mutant allele leads to bone fragility.

Collagen Fibrillogenesis in the Mitral Valve: It’s a Matter of Compliance

Diversity of collagen family members and the closely related collagen-like triple helix-containing proteins found in the mitral valve, will be discussed in addition to how defects in these proteins may lead to valve disease.

References

SHOWING 1-10 OF 15 REFERENCES

Rare autosomal recessive cardiac valvular form of Ehlers-Danlos syndrome results from mutations in the COL1A2 gene that activate the nonsense-mediated RNA decay pathway.

Computer-generated folding of a short stretch of mRNA surrounding the mutation site demonstrated realignment of the relationships between the donor and acceptor sites that could facilitate use of a cryptic donor site, suggesting that folding of the nascent mRNA could be one element that contributes to determination of order of splicing.

Total absence of the α2(I) chain of collagen type I causes a rare form of Ehlers-Danlos syndrome with hypermobility and propensity to cardiac valvular problems

Biochemical analysis of collagens extracted from skin fibroblasts is a powerful tool to detect the subset of patients with complete absence of proα2(I) collagen chains, and in these patients, careful cardiac follow up with ultrasonography is highly recommended because of the risk for cardiac valvular problems in adulthood.

Four patients with Sillence type I osteogenesis imperfecta and mild bone fragility, complicated by left ventricular cardiac valvular disease and cardiac tissue fragility caused by type I collagen mutations

The combined clinical, surgical, histological, ultra‐structural, and molecular genetic data suggest the type I collagen defect as contributory to cardiac valvular disease.

The 2017 international classification of the Ehlers–Danlos syndromes

The International EDS Consortium proposes a revised EDS classification, which recognizes 13 subtypes, and revised the clinical criteria for hypermobile EDS in order to allow for a better distinction from other joint hypermobility disorders.

Ehlers-Danlos syndrome. A variant characterized by the deficiency of pro alpha 2 chain of type I procollagen.

Clinical manifestations characterized by cardiovascular abnormalities due to decreased collagen deposition in the aortic valve and the wall of aorta, hypermobility of the joints, and hyperextensibility of the skin in this patient may be closely related to the observations described above.

Homozygosity for a splice site mutation of the COL1A2gene yields a non-functional proα2(I) chain and an EDS/OI clinical phenotype

Another patient homozygous for a mutation yielding non-functional COL1A2 alleles whose clinical phenotype showed generalised joint hypermobility and foot deformities reminiscent of Ehlers-Danlos syndrome associated with pale blue sclerae and a mild increase in bone fragility characteristic of osteogenesis imperfecta is identified.

Homozygosity by descent for a COL1A2 mutation in two sibs with severe osteogenesis imperfecta and mild clinical expression in the heterozygotes

Abstract We report two sibs with severe, progressively deforming osteogenesis imperfecta (OI) and homozygosity by descent for a glycine 751 to serine substitution in the α2(I) collagen chain due to a

Osteogenesis imperfecta: cloning of a pro-alpha 2(I) collagen gene with a frameshift mutation.

The clinical features of homozygous alpha 2(I) collagen deficient osteogenesis imperfecta.

Clinically, the disease presents as severe progressive Sillence type III osteogenesis imperfecta as the main biochemical defect is the synthesis of an abnormal pro alpha 2(I) chain which does not associate with pro alpha 1(I), therefore is not incorporated into triple helical trimers of type I procollagen which can be used to assemble collagen fibres.