Congenital Defects in a Patient Carrying a Novel Homozygous AEBP1 Variant: Further Expansion of the Phenotypic Spectrum of Ehlers-Danlos Syndrome Classical-like Type 2?
Niccolò Di GiosaffatteAlessandro FerrarisFederica GaudiosoValentina LodatoEmanuele SavinoClaudia CellettiFilippo CamerotaSimone BargiacchiLuigi LainoSilvia MajoreIrene BottilloPaola GrammaticoPublished in: Genes (2022)
In 2018, a new clinical subtype, caused by biallelic variants in the AEBP1 gene, encoding the ACLP protein, was added to the current nosological classification of the Ehlers-Danlos Syndromes (EDS). This new phenotype, provisionally termed EDS classical-like type 2 (clEDS2), has not yet been fully characterized, as only nine cases have been reported to date. Here we describe a patient, homozygous for a novel AEBP1 pathogenic variant (NM_001129.5 c.2123_2124delTG (p.Val708AlafsTer5)), whose phenotype is reminiscent of classical EDS but also includes previously unreported multiple congenital malformations. Furthermore, we briefly summarize the current principal clinical manifestations of clEDS2 and the molecular evidence surrounding the role of AEBP1 in the context of extracellular matrix homeostasis and connective tissue development. Although a different coexisting etiology for the multiple congenital malformations of our patient cannot be formally excluded, the emerging role of ACLP in TGF-β and WNT pathways may explain their occurrence and the phenotypical variability of clEDS2.
Keyphrases
- case report
- extracellular matrix
- copy number
- machine learning
- risk assessment
- deep learning
- photodynamic therapy
- gene expression
- epithelial mesenchymal transition
- intellectual disability
- signaling pathway
- autism spectrum disorder
- small molecule
- genome wide
- transforming growth factor
- dna methylation
- transcription factor