Expanding the clinical and mutational spectrum of recessive AEBP1-related classical-like Ehlers-Danlos syndrome

Marco Ritelli, Valeria Cinquina, Marina Venturini, Letizia Pezzaioli, Anna Maria Formenti, Nicola Chiarelli, Marina Colombi

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article numberE135
Issue number2
Publication statusPublished - 2019


  • AEBP1
  • Aortic carboxypeptidase-like protein
  • Classical Ehlers-Danlos syndrome
  • Classical-like Ehlers-Danlos syndrome type 2
  • Differential diagnosis
  • High-frequency ultrasonography
  • Reflectance confocal microscopy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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