Loss-of-function mutations of CHST14 in a new type of Ehlers-Danlos syndrome

2010 ◽  
Vol 31 (8) ◽  
pp. 966-974 ◽  
Author(s):  
Noriko Miyake ◽  
Tomoki Kosho ◽  
Shuji Mizumoto ◽  
Tatsuya Furuichi ◽  
Atsushi Hatamochi ◽  
...  
Keyword(s):  
Loss Of Function ◽  
Ehlers Danlos Syndrome ◽  
New Type ◽  
Danlos Syndrome

Abstract 333: Vascular Type Ehlers Danlos Syndrome is Associated With Thrombocyte Dysfunction and Low Vitamin D Serum Concentration

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Albert Busch ◽  
Lars Maegdefessel ◽  
René Wildenauer ◽  
Keyword(s):  
Bone Mineralization ◽  
Genetic Disorder ◽  
Coagulation Cascade ◽  
Coagulation Disorders ◽  
Loss Of Function ◽  
Spontaneous Bleeding ◽  
Ehlers Danlos Syndrome ◽  
Vascular Type ◽  
Risk Of Rupture ◽  
Danlos Syndrome

Introduction: The Ehlers-Danlos syndrome is a rare genetic disorder characterized by a heterogeneous mixture of orthopedic, visceral, ophthalmological and vascular affection based on an even broader variety of genetic subtypes. Besides disturbance in all-day life, vascular type EDS often results in life threatening spontaneous bleeding or aneurysm formation with high risk of rupture. Additional impairment of normal hemostasis, especially in emergency scenarios, is suspected. Material and methods: In collaboration with the German National EDS Initiative and funding by the Eva Luise and Horst Köhler Foundation for Rare Diseases, we set up a nationwide screening of blood coagulation tests in vascular type and mixture type EDS patients under normal conditions. Screening was made for blood count, bleeding time, factor XIII, fibrinogen, PFA100, Born aggregometry, ROTEM analysis, C-reactive protein and von Willebrand Factor activity. Results: The genetics of 25 vascular type EDS diagnosed patients in Germany are very heterogeneous, making results difficult to compare. Coagulation disorders of various kinds, however, do appear and affect every aspect of the coagulation cascade. Phenotypes worse within families with clear inheritance patterns suggesting a loss of function. Additionally Vitamin D3 shortage might impair bone mineralization worsening common orthopedic symptoms as well as vascular structural health. Outlook: Decision making for vascular surgery in EDS patients should be made very carefully. A complete coagulation workup together with a hematologist should precede surgery whenever possible. Our study will continue to enroll patients in order to generalize results and verify coagulation disorders.

A new type of Ehlers-Danlos syndrome associated with tortuous systemic arteries?

2007 ◽  
Vol 92 (10) ◽  
pp. 1230-1230
Author(s):  
P Franceschini ◽  
A Guala ◽  
D Licata ◽  
GG Cara ◽  
D Franceschini
Keyword(s):  
Ehlers Danlos Syndrome ◽  
New Type ◽  
Systemic Arteries ◽  
Danlos Syndrome

A new type of Ehlers-Danlos syndrome associated with tortuous systemic arteries in a large kindred from Qatar

2007 ◽  
Vol 92 (4) ◽  
pp. 456-462 ◽  
Author(s):  
A Abdul Wahab ◽  
IA Janahi ◽  
A Eltohami ◽  
A Zeid ◽  
NF Ul Haque ◽  
...  
Keyword(s):  
Ehlers Danlos Syndrome ◽  
New Type ◽  
Systemic Arteries ◽  
Danlos Syndrome

scholarly journals Clinical and molecular features of 66 patients with musculocontractural Ehlers−Danlos syndrome caused by pathogenic variants in CHST14 (mcEDS-CHST14)

2021 ◽  
pp. jmedgenet-2020-107623
Author(s):  
Mari Minatogawa ◽  
Ai Unzaki ◽  
Hiroko Morisaki ◽  
Delfien Syx ◽  
Tohru Sonoda ◽  
...  
Keyword(s):  
Collaborative Study ◽  
Joint Hypermobility ◽  
Loss Of Function ◽  
Multisystem Disorder ◽  
Ehlers Danlos Syndrome ◽  
Molecular Features ◽  
Pathogenic Variants ◽  
International Collaborations ◽  
Delayed Closure ◽  
Danlos Syndrome

BackgroundMusculocontractural Ehlers−Danlos syndrome is caused by biallelic loss-of-function variants in CHST14 (mcEDS-CHST14) or DSE (mcEDS-DSE). Although 48 patients in 33 families with mcEDS-CHST14 have been reported, the spectrum of pathogenic variants, accurate prevalence of various manifestations and detailed natural history have not been systematically investigated.MethodsWe collected detailed and comprehensive clinical and molecular information regarding previously reported and newly identified patients with mcEDS-CHST14 through international collaborations.ResultsSixty-six patients in 48 families (33 males/females; 0–59 years), including 18 newly reported patients, were evaluated. Japanese was the predominant ethnicity (27 families), associated with three recurrent variants. No apparent genotype–phenotype correlation was noted. Specific craniofacial (large fontanelle with delayed closure, downslanting palpebral fissures and hypertelorism), skeletal (characteristic finger morphologies, joint hypermobility, multiple congenital contractures, progressive talipes deformities and recurrent joint dislocation), cutaneous (hyperextensibility, fine/acrogeria-like/wrinkling palmar creases and bruisability) and ocular (refractive errors) features were observed in most patients (>90%). Large subcutaneous haematomas, constipation, cryptorchidism, hypotonia and motor developmental delay were also common (>80%). Median ages at the initial episode of dislocation or large subcutaneous haematoma were both 6 years. Nine patients died; their median age was 12 years. Several features, including joint and skin characteristics (hypermobility/extensibility and fragility), were significantly more frequent in patients with mcEDS-CHST14 than in eight reported patients with mcEDS-DSE.ConclusionThis first international collaborative study of mcEDS-CHST14 demonstrated that the subtype represents a multisystem disorder with unique set of clinical phenotypes consisting of multiple malformations and progressive fragility-related manifestations; these require lifelong, multidisciplinary healthcare approaches.

A new type of Ehlers-Danlos syndrome associated with tortuous systemic arteries in a large kindred from Qatar Reply

2007 ◽  
Vol 92 (10) ◽  
pp. 1230-1230
Author(s):  
P Franceschini ◽  
A Guala ◽  
D Licata ◽  
GG Cara ◽  
D Franceschini
Keyword(s):  
Ehlers Danlos Syndrome ◽  
New Type ◽  
Systemic Arteries ◽  
Danlos Syndrome

Systematic investigation of the skin in Chst14−/− mice: A model for skin fragility in musculocontractural Ehlers–Danlos syndrome caused by CHST14 variants (mcEDS-CHST14)

Glycobiology ◽  
2020 ◽  
Author(s):  
Takuya Hirose ◽  
Shuji Mizumoto ◽  
Ayana Hashimoto ◽  
Yuki Takahashi ◽  
Takahiro Yoshizawa ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Anion Exchange ◽  
Dermatan Sulfate ◽  
Systematic Investigation ◽  
Exchange Chromatography ◽  
Collagen Fibrils ◽  
Loss Of Function ◽  
Ehlers Danlos Syndrome ◽  
Skin Fragility ◽  
Danlos Syndrome

Abstract Loss-of-function variants in CHST14 cause a dermatan 4-O-sulfotransferase deficiency named musculocontractural Ehlers–Danlos syndrome-CHST14 (mcEDS-CHST14), resulting in complete depletion of the dermatan sulfate moiety of decorin glycosaminoglycan (GAG) chains, which is replaced by chondroitin sulfate. Recently, we uncovered structural alteration of GAG chains in the skin of patients with mcEDS-CHST14. Here, we conducted the first systematic investigation of Chst14 gene-deleted homozygote (Chst14−/−) mice. We used skin samples of wild-type (Chst14+/+) and Chst14−/− mice. Mechanical fragility of the skin was measured with a tensile test. Pathology was observed using light microscopy, decorin immunohistochemistry and electron microscopy (EM) including cupromeronic blue (CB) staining. Quantification of chondroitin sulfate and dermatan sulfate was performed using enzymatic digestion followed by anion-exchange HPLC. In Chst14−/− mice, skin tensile strength was significantly decreased compared with that in Chst14+/+ mice. EM showed that collagen fibrils were oriented in various directions to form disorganized collagen fibers in the reticular layer. Through EM-based CB staining, rod-shaped linear GAG chains were found to be attached at one end to collagen fibrils and protruded outside of the fibrils, in contrast to them being round and wrapping the collagen fibrils in Chst14+/+ mice. A very low level of dermatan sulfate disaccharides was detected in the skin of Chst14−/− mice by anion-exchange chromatography. Chst14−/− mice, exhibiting similar abnormalities in the GAG structure of decorin and collagen networks in the skin, could be a reasonable model for skin fragility of patients with mcEDS-CHST14, shedding light on the role of dermatan sulfate in maintaining skin strength.

Ehlers-Danlos Syndrome, Kyphoscoliotic Type (Formerly Type VI) as Differential Diagnosis to Neuromuscular Diseases

2016 ◽  
Vol 47 (S 01) ◽  
Author(s):  
M. Schroth ◽  
C. Reihle ◽  
M. Wachowsky ◽  
L. Travan ◽  
M. Buob ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Neuromuscular Diseases ◽  
Ehlers Danlos Syndrome ◽  
Danlos Syndrome
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