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.
| Original language | English |
|---|---|
| Article number | 135 |
| Journal | Genes |
| Volume | 10 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
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Keywords
- 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)
Cite this
Expanding the clinical and mutational spectrum of recessive AEBP1-related classical-like Ehlers-Danlos syndrome. / Ritelli, Marco; Cinquina, Valeria; Venturini, Marina; Pezzaioli, Letizia; Formenti, Anna Maria; Chiarelli, Nicola; Colombi, Marina.
In: Genes, Vol. 10, No. 2, 135, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expanding the clinical and mutational spectrum of recessive AEBP1-related classical-like Ehlers-Danlos syndrome
AU - Ritelli, Marco
AU - Cinquina, Valeria
AU - Venturini, Marina
AU - Pezzaioli, Letizia
AU - Formenti, Anna Maria
AU - Chiarelli, Nicola
AU - Colombi, Marina
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - AEBP1
KW - Aortic carboxypeptidase-like protein
KW - Classical Ehlers-Danlos syndrome
KW - Classical-like Ehlers-Danlos syndrome type 2
KW - Differential diagnosis
KW - High-frequency ultrasonography
KW - Reflectance confocal microscopy
UR - http://www.scopus.com/inward/record.url?scp=85062324141&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062324141&partnerID=8YFLogxK
U2 - 10.3390/genes10020135
DO - 10.3390/genes10020135
M3 - Article
AN - SCOPUS:85062324141
VL - 10
JO - Genes
JF - Genes
SN - 2073-4425
IS - 2
M1 - 135
ER -