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Open AccessArticle

Further Defining the Phenotypic Spectrum of B3GAT3 Mutations and Literature Review on Linkeropathy Syndromes

1
Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
2
Genetics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy
3
Division of Dermatology, Department of Clinical and Experimental Sciences, Spedali Civili University Hospital, 25123 Brescia, Italy
*
Author to whom correspondence should be addressed.
Genes 2019, 10(9), 631; https://doi.org/10.3390/genes10090631
Received: 25 June 2019 / Revised: 9 August 2019 / Accepted: 19 August 2019 / Published: 21 August 2019
The term linkeropathies (LKs) refers to a group of rare heritable connective tissue disorders, characterized by a variable degree of short stature, skeletal dysplasia, joint laxity, cutaneous anomalies, dysmorphism, heart malformation, and developmental delay. The LK genes encode for enzymes that add glycosaminoglycan chains onto proteoglycans via a common tetrasaccharide linker region. Biallelic variants in XYLT1 and XYLT2, encoding xylosyltransferases, are associated with Desbuquois dysplasia type 2 and spondylo-ocular syndrome, respectively. Defects in B4GALT7 and B3GALT6, encoding galactosyltransferases, lead to spondylodysplastic Ehlers-Danlos syndrome (spEDS). Mutations in B3GAT3, encoding a glucuronyltransferase, were described in 25 patients from 12 families with variable phenotypes resembling Larsen, Antley-Bixler, Shprintzen-Goldberg, and Geroderma osteodysplastica syndromes. Herein, we report on a 13-year-old girl with a clinical presentation suggestive of spEDS, according to the 2017 EDS nosology, in whom compound heterozygosity for two B3GAT3 likely pathogenic variants was identified. We review the spectrum of B3GAT3-related disorders and provide a comparison of all LK patients reported up to now, highlighting that LKs are a phenotypic continuum bridging EDS and skeletal disorders, hence offering future nosologic perspectives. View Full-Text
Keywords: linkeropathies; B3GAT3; Larsen-like syndrome; B4GALT7; B3GALT6; spondylodysplastic Ehlers-Danlos syndrome; XYLT1; XYLT2; Desbuquois dysplasia; spondylo-ocular syndrome linkeropathies; B3GAT3; Larsen-like syndrome; B4GALT7; B3GALT6; spondylodysplastic Ehlers-Danlos syndrome; XYLT1; XYLT2; Desbuquois dysplasia; spondylo-ocular syndrome
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Ritelli, M.; Cinquina, V.; Giacopuzzi, E.; Venturini, M.; Chiarelli, N.; Colombi, M. Further Defining the Phenotypic Spectrum of B3GAT3 Mutations and Literature Review on Linkeropathy Syndromes. Genes 2019, 10, 631.

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