2. Academic Validation
  3. Mutations in B3GALT6, which encodes a glycosaminoglycan linker region enzyme, cause a spectrum of skeletal and connective tissue disorders

Mutations in B3GALT6, which encodes a glycosaminoglycan linker region enzyme, cause a spectrum of skeletal and connective tissue disorders

  • Am J Hum Genet. 2013 Jun 6;92(6):927-34. doi: 10.1016/j.ajhg.2013.04.003.
Masahiro Nakajima 1,  Shuji Mizumoto,  Noriko Miyake,  Ryo Kogawa,  Aritoshi Iida,  Hironori Ito,  Hiroshi Kitoh,  Aya Hirayama,  Hiroshi Mitsubuchi,  Osamu Miyazaki,  Rika Kosaki,  Reiko Horikawa,  Angeline Lai,  Roberto Mendoza-Londono,  Lucie Dupuis,  David Chitayat,  Andrew Howard,  Gabriela F Leal,  Denise Cavalcanti,  Yoshinori Tsurusaki,  Hirotomo Saitsu,  Shigehiko Watanabe,  Ekkehart Lausch,  Sheila Unger,  Luisa Bonafé,  Hirofumi Ohashi,  Andrea Superti-Furga,  Naomichi Matsumoto,  Kazuyuki Sugahara,  Gen Nishimura,  Shiro Ikegawa
Affiliations

Affiliation

  • 1 Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo 108-8639, Japan.
PMID: 23664117 DOI: 10.1016/j.ajhg.2013.04.003
Abstract

Proteoglycans (PGs) are a major component of the extracellular matrix in many tissues and function as structural and regulatory molecules. PGs are composed of core proteins and glycosaminoglycan (GAG) side chains. The biosynthesis of GAGs starts with the linker region that consists of four sugar residues and is followed by repeating disaccharide units. By exome Sequencing, we found that B3GALT6 encoding an Enzyme involved in the biosynthesis of the GAG linker region is responsible for a severe skeletal dysplasia, spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMD-JL1). B3GALT6 loss-of-function mutations were found in individuals with SEMD-JL1 from seven families. In a subsequent candidate gene study based on the phenotypic similarity, we found that B3GALT6 is also responsible for a connective tissue disease, Ehlers-Danlos syndrome (progeroid form). Recessive loss-of-function mutations in B3GALT6 result in a spectrum of disorders affecting a broad range of skeletal and connective tissues characterized by lax skin, muscle hypotonia, joint dislocation, and spinal deformity. The pleiotropic phenotypes of the disorders indicate that B3GALT6 plays a critical role in a wide range of biological processes in various tissues, including skin, bone, cartilage, tendon, and ligament.

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