Expanding the Clinical and Mutational Spectrum of Recessive AEBP1-Related Classical-Like Ehlers-Danlos Syndrome
Open accessAbstract
Ehlers-Danlos syndrome (EDS) comprises clinically heterogeneous connective tissue disorders with diverse molecular etiologies. The 2017 International Classification for EDS recognized 13 distinct subtypes caused by pathogenic variants in 19 genes mainly encoding fibrillar collagens and collagen-modifying or processing proteins. Recently, a new EDS subtype, i.e., classical-like EDS type 2, was defined after the identification, in six patients with clinical findings reminiscent of EDS, of recessive alterations in AEBP1, which encodes the aortic carboxypeptidase–like protein associating with collagens in the extracellular matrix. Herein, we report on a 53-year-old patient, born from healthy second-cousins, who fitted the diagnostic criteria for classical EDS (cEDS) for the presence of hyperextensible skin with multiple atrophic scars, generalized joint hypermobility, and other minor criteria. Molecular analyses of cEDS genes did not identify any causal variant. Therefore, AEBP1 sequencing was performed that revealed homozygosity for the rare c.1925T>C p.(Leu642Pro) variant classified as likely pathogenetic (class 4) according to the American College of Medical Genetics and Genomics (ACMG) guidelines. The comparison of the patient’s features with those of the other patients reported up to now and the identification of the first missense variant likely associated with the condition offer future perspectives for EDS nosology and research in this field.
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A new and very rare EDS variant is caused by biallelic mutations in the AEBP1 gene.
“Recently, a new and very rare EDS variant has been identified that is caused by biallelic mutations in the AEBP1 gene (Table 1) [33,34,35,36].”
From Cellular and Molecular Mechanisms in the Pathogenesis of Classical, Vascular, and Hypermobile Ehlers‒Danlos Syndromes (2019) · cites this paper as [36]
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Chiarelli, N., Ritelli, M., Zoppi, N., & Colombi, M. (2019) · Genes · doi:10.3390/genes10080609 · Cited by 82 · see citing works
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- Authors
- Ritelli, M., Cinquina, V., Venturini, M., Pezzaioli, L., Formenti, A. M., Chiarelli, N., & Colombi, M.
- Affiliations
- University of Brescia (IT)
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT)
- IRCCS Ospedale Galeazzi - Sant'Ambrogio (IT)
- Corresponding author
- Colombi, Marina
- ORCID
- Venue
- Genes
- Publisher
- MDPI AG
- Published
- 2019-02-12
- Volume
- 10
- Issue
- 2
- Pages
- 135
- ISSN
- 2073-4425 (ISSN-L)
- PMC
- PMC6410021
- OpenAlex
- W2912467266
- Cited by
- 33
- References
- 42
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 8 · 2023: 6 · 2022: 3 · 2021: 3 · 2020: 6 · 2019: 3
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Genes (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
- Keywords
- Ehlers-Danlos syndrome, AEBP1, recessive inheritance, missense mutations, connective tissue diseases, collagen processing, joint hypermobility, atrophic scars, homozygous variant
- MeSH terms
- Adolescent, Carboxypeptidases, Collagen, Ehlers-Danlos Syndrome, Extracellular Matrix, Female, Genetic Testing, Homozygote, Humans, Middle Aged, Mutation, Repressor Proteins, Collagen Type V
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