TY - JOUR
T1 - COL1-Related Disorders: Case Report and Review of Overlapping Syndromes
AU - Gnoli, Maria
AU - Brizola, Evelise
AU - Tremosini, Morena
AU - Pedrini, Elena
AU - Maioli, Margherita
AU - Mosca, Massimiliano
AU - Bassotti, Alessandra
AU - Castronovo, Paola
AU - Giunta, Cecilia
AU - Sangiorgi, Luca
N1 - Copyright © 2021 Gnoli, Brizola, Tremosini, Pedrini, Maioli, Mosca, Bassotti, Castronovo, Giunta and Sangiorgi.
PY - 2021/5/7
Y1 - 2021/5/7
N2 - Collagen type I mutations are related to wide phenotypic expressions frequently causing an overlap of clinical manifestations, in particular between Osteogenesis Imperfecta (OI) and Ehlers-Danlos syndrome (EDS). Both disorders present inter- and intra-familial clinical variability and several clinical signs are present in both diseases. Recently, after the observation that some individuals first ascertained by a suspicion of EDS resulted then carriers of pathogenic variants of genes known to primarily cause OI, some authors proposed the term "COL1-related overlap disorder" to describe these cases. In this paper, we report clinical, molecular, and biochemical information about an individual with a diagnosis of EDS with severe joint hypermobility who carries a pathogenic heterozygous variant in COL1A2 gene, and a benign variant in COL1A1 gene. The pathogenic variant, commonly ascribed to OI, as well as the benign variant, has been inherited from the individual's mother, who presented only mild signs of OI and the diagnosis of OI was confirmed only after molecular testing. In addition, we reviewed the literature of similar cases of overlapping syndromes caused by COL1 gene mutations. The reported case and the literature review suggest that the COL1-related overlap disorders (OI, EDS and overlapping syndromes) represent a continuum of clinical phenotypes related to collagen type I mutations. The spectrum of COL1-related clinical manifestations, the pathophysiology and the underlying molecular mechanisms support the adoption of the updated proposed term "COL1-related overlap disorder" to describe the overlapping syndromes.
AB - Collagen type I mutations are related to wide phenotypic expressions frequently causing an overlap of clinical manifestations, in particular between Osteogenesis Imperfecta (OI) and Ehlers-Danlos syndrome (EDS). Both disorders present inter- and intra-familial clinical variability and several clinical signs are present in both diseases. Recently, after the observation that some individuals first ascertained by a suspicion of EDS resulted then carriers of pathogenic variants of genes known to primarily cause OI, some authors proposed the term "COL1-related overlap disorder" to describe these cases. In this paper, we report clinical, molecular, and biochemical information about an individual with a diagnosis of EDS with severe joint hypermobility who carries a pathogenic heterozygous variant in COL1A2 gene, and a benign variant in COL1A1 gene. The pathogenic variant, commonly ascribed to OI, as well as the benign variant, has been inherited from the individual's mother, who presented only mild signs of OI and the diagnosis of OI was confirmed only after molecular testing. In addition, we reviewed the literature of similar cases of overlapping syndromes caused by COL1 gene mutations. The reported case and the literature review suggest that the COL1-related overlap disorders (OI, EDS and overlapping syndromes) represent a continuum of clinical phenotypes related to collagen type I mutations. The spectrum of COL1-related clinical manifestations, the pathophysiology and the underlying molecular mechanisms support the adoption of the updated proposed term "COL1-related overlap disorder" to describe the overlapping syndromes.
KW - COL1
KW - clinical signs
KW - collagen
KW - collagen type I
KW - musculoskeletal diseases
KW - overlap
KW - rare diseases
U2 - 10.3389/fgene.2021.640558
DO - 10.3389/fgene.2021.640558
M3 - Article
C2 - 34025714
VL - 12
SP - 1
EP - 8
JO - Front. Genet.
JF - Front. Genet.
SN - 1664-8021
ER -