Further defining the phenotypic spectrum ofB4GALT7mutations

Abstract

Proteoglycans are components of the extracellular matrix with diverse biological functions. Defects in proteoglycan synthesis have been linked to several human diseases with common features of short stature, hypermobility, joint dislocations, and skeletal dysplasia. B4GALT7 encodes galactosyltransferase-I that catalyzes the addition of a galactose moiety to a xylosyl group in the tetrasaccharide linker of proteoglycans. Mutations in this gene have been associated with the rare progeroid form of Ehlers Danlos syndrome and in addition more recently found to underlie Larsen of Reunion Island syndrome. Nine individuals have been reported with a diagnosis of the progeroid form of Ehlers Danlos syndrome, four of whom have had molecular characterization showing homozygous or compound heterozygous mutations in B4GALT7. We report two newly described patients with compound heterozygous mutations in B4GALT7, and show that the six individuals with confirmed mutations do not have the progeroid features described in the original five patients with a clinical diagnosis of the progeroid form of Ehlers Danlos syndrome. We suggest that galactosyltransferase-I deficiency does not cause the progeroid form of Ehlers Danlos syndrome, but instead results in a clinically recognizable syndrome comprising short stature, joint hypermobility, radioulnar synostosis, and severe hypermetropia. This group of syndromic patients are on a phenotypic spectrum with individuals who have Larsen of Reunion Island syndrome, although the key features of osteopenia, fractures and hypermetropia have not been reported in patients from Reunion Island. © 2016 Wiley Periodicals, Inc.

Chondrodysplasia with multiple dislocations: comprehensive study of a series of 30 cases

“…Those conditions share overlapping features, i.e. Moreover, hand signs are insufficient to orient the diagnosis: B4GALT7 cases can have brachymesophalangy of 2-4 fingers, and show frequent phalangeal dislocations or bifid thumb, but some have no specific hand features (10,37). Moreover, hand signs are insufficient to orient the diagnosis: B4GALT7 cases can have brachymesophalangy of 2-4 fingers, and show frequent phalangeal dislocations or bifid thumb, but some have no specific hand features (10,37).…”

Genetic testing for the diagnosis and classification of joint hypermobility: a case report of 15 patients

“…The boy presented with marked generalized joint hypermobility, scoliosis, cryptorchidism, hypotonia, pectus carinatum and craniofacial dysmorphism, he also had some atrophic scarring on his arms and legs. When firstly referred to our hospital, we diagnosed him as progeroid-type EDS according to the characteristic clinical features [18][19][20], which changed its name as spondylodysplastic EDS (spEDS) [3,19,21], and caused by B4GALT7 or B3GALT6…”

Corneal clouding, cataract, and colobomas with a novel missense mutation inB4GALT7—a review of eye anomalies in the linkeropathy syndromes

“…Proteoglycans (PGs) are cell surface molecules that are essential components of the extracellular matrix and that regulate numerous cellular processes, including cell adhesion, migration, proliferation, differentiation and cell‐cell and cell‐matrix interactions [Guo et al, ; von Oettingen et al, ; Jones et al, ; Salter et al, ]. They consist of a core protein with one or more specific glycosaminoglycan (GAG) side chains that are highly hydrophilic to help impart volume and elasticity to tissues [Guo et al, ].…”

“…They consist of a core protein with one or more specific glycosaminoglycan (GAG) side chains that are highly hydrophilic to help impart volume and elasticity to tissues [Guo et al, ]. The GAG side chains are attached to a serine residue via a tetrasaccharide linkage region that is common to all GAGs and formed by the serial addition of one xylose, two galactoses, and one glucuronic acid moiety (GlcUA‐Gal‐Gal‐Xyl) [Miyake et al, ; von Oettingen et al, ; Salter et al, ]. For the formation of the tetrasaccharide linkage region, the first reaction transfers xylose from uridine diphosphate‐xylose (UDP‐Xyl) to specific serine residues of the PGs core protein and is mediated by xylosyltransferases I and II, encoded by XYLT1 (MIM 608124) [Bui et al, ; Schreml et al, ] and XYLT2 (MIM 6081250) [Taylan et al, ].…”

“…Linkeropathies share specific phenotypic findings, comprising short stature, joint laxity/hypermobility with joint dislocations, dysmorphic facial features with brachycephaly, a prominent forehead, proptosis and a small mouth, and skeletal anomalies that include radio‐ulnar synostosis, decreased bone density, and broad digit tips [Jones et al, ]. Other frequent findings are congenital contractures, a short or broad neck, congenital heart defects, hypotonia, and developmental delays [Jones et al, ; Salter et al, ].…”