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Genes 2019, 10(2), 135; https://doi.org/10.3390/genes10020135

Expanding the Clinical and Mutational Spectrum of Recessive AEBP1-Related Classical-Like Ehlers-Danlos Syndrome

1
Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
2
Division of Dermatology, Department of Clinical and Experimental Sciences, Spedali Civili University Hospital, 25123 Brescia, Italy
3
Spedali Civili of Brescia, 25123 Brescia, Italy
4
IRCCS Istituto Ortopedico Galeazzi, 20161 Milano, Italy
*
Author to whom correspondence should be addressed.
Received: 10 January 2019 / Revised: 28 January 2019 / Accepted: 8 February 2019 / Published: 12 February 2019
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Abstract

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. View Full-Text
Keywords: classical Ehlers-Danlos syndrome; classical-like Ehlers-Danlos syndrome type 2; AEBP1; aortic carboxypeptidase-like protein; differential diagnosis; high-frequency ultrasonography; reflectance confocal microscopy classical Ehlers-Danlos syndrome; classical-like Ehlers-Danlos syndrome type 2; AEBP1; aortic carboxypeptidase-like protein; differential diagnosis; high-frequency ultrasonography; reflectance confocal microscopy
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Ritelli, M.; Cinquina, V.; Venturini, M.; Pezzaioli, L.; Formenti, A.M.; Chiarelli, N.; Colombi, M. Expanding the Clinical and Mutational Spectrum of Recessive AEBP1-Related Classical-Like Ehlers-Danlos Syndrome. Genes 2019, 10, 135.

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