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A homozygous B3GAT3 mutation causes a severe syndrome with multiple fractures, expanding the phenotype of linkeropathy syndromes. Am J Med Genet A 2015 Nov;167A(11):2691-6

Date

06/19/2015

Pubmed ID

26086840

Pubmed Central ID

PMC4654953

DOI

10.1002/ajmg.a.37209

Scopus ID

2-s2.0-84947029770 (requires institutional sign-in at Scopus site)   40 Citations

Abstract

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 B3GAT3, adds the last four saccharides comprising the linker region. Mutations in B3GAT3 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 B3GAT3 (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 B3GAT3 mutations and a provide comparative overview of the phenotypic features of the linkeropathies associated with mutations in XYLT1, B4GALT7, B3GALT6, and B3GAT3.

Author List

Jones KL, Schwarze U, Adam MP, Byers PH, Mefford HC

Author

Kelly Jones MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Fractures, Multiple
Genetic Testing
Glucuronosyltransferase
Homozygote
Humans
Infant
Infant, Newborn
Male
Mutation
Phenotype
Radiography
Syndrome