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Cited by 124Connective tissue disorders researchDermatological and Skeletal DisordersCollagen: Extraction and Characterization

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

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Malfait, F, Symoens, S, Coucke, P, Nunes, L, De Almeida, S, De Paepe, A·2006·Journal of Medical Genetics
DOI 10.1136/jmg.2005.038224PMC PMC2564565
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Abstract

Background: Heterozygous mutations in the COL1A1 or COL1A2 gene encoding the α1 and α2 chain of type I collagen generally cause either osteogenesis imperfecta or the arthrochalasis form of Ehlers-Danlos syndrome (EDS). Homozygous or compound heterozygous COL1A2 mutations resulting in complete deficiency of the proα2(I) collagen chains are extremely rare and have been reported in only a few patients, albeit with variable phenotypic outcome. Methods: The clinical features of the proband, a 6 year old boy, were recorded. Analysis of proα and α-collagen chains was performed by SDS-polyacrylamide gel electrophoresis using the Laemmli buffer system. Single stranded conformation polymorphism analysis of the proband’s DNA was also carried out. Results: In this report we show that complete lack of proα2(I) collagen chains can present as a phenotype reminiscent of mild hypermobility EDS during childhood. Conclusions: 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.

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  • In cardiac-valvular EDS, SDS PAGE demonstrates complete absence of (pro-)α2 chains of type I (pro)collagen extracted from dermis.

    “SDS PAGE demonstrates complete absence of (pro-) a 2 chains of type I (pro) collagen extracted from dermis [Schwarze et al., 2004; Malfait et al., 2006].”

    From The 2017 international classification of the Ehlers–Danlos syndromes (2017) · cites this paper as Malfait et al., 2006

  • In the two reported children (with the condition under discussion), there were no severe cardiovascular features, although mitral valve bulging was noted in one.

    “The two reported children had no severe cardiovascular features, although mitral valve bulging was noted in one [Nicholls et al., 2001;Malfait et al., 2006].”

    From The Ehlers–Danlos syndromes, rare types (2017) · cites this paper as Malfait et al., 2006

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Research works printed but not linked: 16

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  2. Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers- Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). Am J Med Genet 1998;77(1):31-7.
  3. Malfait F, De Coster P, Hausser I, van Essen AJ, Franck P, Colige A, Nusgens B, Martens L, De Paepe A. The natural history, including orofacial features of three patients with Ehlers-Danlos syndrome, dermatosparaxis type (EDS type VIIC). Am J Med Genet 2004;131(1):18-28.
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  7. Pihlajaniemi T, Dickson LA, Pope FM, Korhonen VR, Nicholls A, Prockop DJ, Myers JC. Osteogenesis imperfecta: cloning of a pro-alpha 2(I) collagen gene with a frameshift mutation. J Biol Chem 1984;259(21):12941-4.
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  10. Nicholls AC, Valler D, Wallis S, Pope FM. Homozygosity for a splice site mutation of the COL1A2 gene yields a non-functional pro(alpha)2(I) chain and an EDS/OI clinical phenotype. J Med Genet 2001;38(2):132-6.
  11. Schwarze U, Hata R, McKusick VA, Shinkai H, Hoyme HE, Pyeritz RE, Byers PH. 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. Am J Hum Genet 2004;74(5):917-30.
  12. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970;227(259):680-5.
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Authors
Malfait, F., Symoens, S., Coucke, P., Nunes, L., De Almeida, S., & De Paepe, A.
Affiliations
  • Ghent University Hospital (BE)
  • Hospital de Dona Estefânia (PT)
ORCID
Venue
Journal of Medical Genetics
Publisher
BMJ
Published
2006-06-30
Volume
43
Issue
7
Pages
e36-e36
ISSN
  • 0022-2593 (ISSN-L)
  • 1468-6244
DOI
10.1136/jmg.2005.038224
PMC
PMC2564565
OpenAlex
W2152659758
Cited by
124
References
2
Citations by year
2026: 4 · 2025: 7 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 7 · 2019: 7 · 2018: 4 · 2017: 16 · 2016: 4 · 2015: 5 · 2014: 5 · 2013: 11 · 2012: 7
FWCI
2.47
Type
journal article
Language
en
Open access
Locations
  • Journal of Medical Genetics (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
  • Physical Sciences › Materials Science › Biomaterials › Collagen: Extraction and Characterization
Keywords
Ehlers-Danlos syndrome, hypermobility type, type I collagen, COL1A2 mutation, homozygous mutation, valvular heart disease, connective tissue diseases, dermal fibroblasts, pediatric patients
MeSH terms
Child, Collagen, Consanguinity, Ehlers-Danlos Syndrome, Female, Foot Deformities, Hand Deformities, Heart Valve Diseases, Humans, Male, Motor Activity, Gene Deletion, Polymorphism, Single-Stranded Conformational, Genetic Predisposition to Disease, Collagen Type I

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