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Further defining the phenotypic spectrum of B4GALT7 mutations

Further defining the phenotypic spectrum of B4GALT7 mutations
Further defining the phenotypic spectrum of B4GALT7 mutations
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.
progeroid ehlers danlos syndrome, b4galt7, linkeropathy, proteoglycans, galactosyltransferases
1552-4825
1556-1563
Salter, Claire G.
e7908fa1-57b1-4d14-82eb-14e465b19c42
Davies, Justin H.
9f18fcad-f488-4c72-ac23-c154995443a9
Moon, Rebecca J.
954fb3ed-9934-4649-886d-f65944985a6b
Fairhurst, Joanna
2812ed8e-8598-49bc-8919-52fecd2c0fef
Bunyan, David
d57bd2a7-d531-4892-bcce-e096dc95eee7
Foulds, Nicola
5e153e9f-caae-45f5-b6f0-943bd567558e
Salter, Claire G.
e7908fa1-57b1-4d14-82eb-14e465b19c42
Davies, Justin H.
9f18fcad-f488-4c72-ac23-c154995443a9
Moon, Rebecca J.
954fb3ed-9934-4649-886d-f65944985a6b
Fairhurst, Joanna
2812ed8e-8598-49bc-8919-52fecd2c0fef
Bunyan, David
d57bd2a7-d531-4892-bcce-e096dc95eee7
Foulds, Nicola
5e153e9f-caae-45f5-b6f0-943bd567558e

Salter, Claire G., Davies, Justin H., Moon, Rebecca J., Fairhurst, Joanna, Bunyan, David and Foulds, Nicola (2016) Further defining the phenotypic spectrum of B4GALT7 mutations. American Journal of Medical Genetics: Part A, 170 (6), 1556-1563. (doi:10.1002/ajmg.a.37604). (PMID:26940150)

Record type: Article

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.

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More information

Accepted/In Press date: 4 February 2016
e-pub ahead of print date: 4 March 2016
Published date: June 2016
Keywords: progeroid ehlers danlos syndrome, b4galt7, linkeropathy, proteoglycans, galactosyltransferases
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 389801
URI: http://eprints.soton.ac.uk/id/eprint/389801
ISSN: 1552-4825
PURE UUID: ef94c3f3-9198-4147-8568-b56bc5c09a7e

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Date deposited: 15 Mar 2016 15:29
Last modified: 15 Jul 2019 20:41

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Contributors

Author: Claire G. Salter
Author: Rebecca J. Moon
Author: Joanna Fairhurst
Author: David Bunyan
Author: Nicola Foulds

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