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Am J Med Genet A. 2016 Jun;170(6):1556-63. doi: 10.1002/ajmg.a.37604. Epub 2016 Mar 4.

Further defining the phenotypic spectrum of B4GALT7 mutations.

Author information

1
West Midlands Regional Genetics Service, Birmingham Women's Hospital NHS Foundation Trust, Birmingham, United Kingdom.
2
Paediatric Endocrinology, University Hospitals Southampton NHS Foundation Trust, United Kingdom.
3
Paediatric Radiology, University Hospitals Southampton NHS Foundation Trust, United Kingdom.
4
Wessex Regional Genetics Services, Salisbury District Hospital, United Kingdom.
5
Wessex Clinical Genetics Service, University Hospitals Southampton NHS Foundation Trust, United Kingdom.

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.

KEYWORDS:

B4GALT7; galactosyltransferases; linkeropathy; progeroid Ehlers Danlos syndrome; proteoglycans

PMID:
26940150
DOI:
10.1002/ajmg.a.37604
[Indexed for MEDLINE]

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