A homozygous B3GAT3 mutation causes a severe syndrome with multiple fractures, expanding the phenotype of linkeropathy syndromes. (18th June 2015)

• Record Type: Journal Article
• Authors: Jones, Kelly L.; Schwarze, Ulrike; Adam, Margaret P.; Byers, Peter H.; Mefford, Heather C.
• Is Part Of: American journal of medical genetics. Volume 167:Number 11(2015:Nov.)
• Page Start: 2691
• Page End: 2696
• Publication Date: 2015-06-18
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.37209
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga37209-sec-0001" sec-type="section"> <p>Linkeropathies are a group of syndromes characterized by short stature, radio‐ulnar synostosis, decreased bone density, congenital contractures and dislocations, joint laxity, broad digits, brachycephaly, small mouth, prominent eyes, short or webbed neck, congenital heart defects and mild developmental delay. Linkeropathies are due to enzymatic defects in the synthesis of the common linker region that joins the core proteins to their glycosaminoglycan (GAG) side chains. The enzyme glucuronyltransferase 1, encoded by <italic>B3GAT3</italic>, adds the last four saccharides comprising the linker region. Mutations in <italic>B3GAT3</italic> have been reported in two unrelated families with the same homozygous mutation (c.830G>A, p.Arg277Gln). We report on a patient with a novel homozygous <italic>B3GAT3</italic> (c.667G>A, p.Gly223Ser) mutation and a history of multiple fractures, blue sclerae, and glaucoma. Our patient was a 12‐month‐old boy born to consanguineous parents and, like previously reported patients, he had bilateral radio‐ulnar synostosis, severe osteopenia, an increased gap between first and second toes, bilateral club feet, and atrial and ventricular septal defects. He had the additional features of bilateral glaucoma, hypertelorism, upturned nose with anteverted nares, a small chest, a diaphragmatic hernia, multiple fractures, arachnodactyly, overlapping fingers with ulnar deviation, lymphedema, hypotonia, hearing loss, and perinatal cerebral infarction with bilateral supra‐ and infratentorial subdural hematomas. We highlight the extended phenotypic range of <italic>B3GAT3</italic> mutations and a provide comparative overview of the phenotypic features of the linkeropathies associated with mutations in <italic>XYLT1</italic>, <italic>B4GALT7</italic>, <italic>B3GALT6</italic>, and <italic>B3GAT3</italic>. © 2015 Wiley Periodicals, Inc.</p> </sec> </abstract>