Protein O-mannosyltransferase activities in lymphoblasts from patients with α-dystroglycanopathies

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• 作者：Hiroshi Manya ; Cé ; line Bouchet ; Akiko Yanagisawa ; S ; rine Vuillaumier-Barrot ; Susana Quijano-Roy ; Yasushi Suzuki ; Svetlana Maugenre ; Pascale Richard ; Toshiyuki Inazu ; Luciano Merlini ; Norma B. Rome
• 关键词：POMT1 ; POMT2 ; POMGnT1 ; Congenital muscular dystrophy ; Enzyme activity
• 刊名：Neuromuscular Disorders
• 出版年：2008
• 出版时间：January 2008
• 年：2008
• 卷：18
• 期：1
• 页码：45-51
• 全文大小：160 K

文摘

Defects in O-mannosylation of α-dystroglycan cause some forms of congenital muscular dystrophy (CMD), the so-called α-dystroglycanopathies. Six genes are responsible for these diseases with overlapping phenotypes.

We investigated the usefulness of a biochemical approach for the diagnosis and investigation of the α-dystroglycanopathies using immortalized lymphoblasts prepared from genetically diagnosed and undiagnosed CMD patients and from control subjects. We measured the activities of protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) and protein O-mannosyltransferase (POMT). Lymphoblasts from patients harbouring known mutations in either POMGNT1 or POMT1 showed a marked decrease in POMGnT1 or POMT activity, respectively, compared to controls. Furthermore, we identified pathogenic mutations in POMGNT1, POMT1 or POMT2 in six previously genetically uncharacterised patients who had very low enzyme activity. In conclusion, the lymphoblast-based enzymatic assay is a sensitive and useful method (i) to select patients harbouring POMGNT1, POMT1 or POMT2 mutations; (ii) to assess the pathogenicity of new or already described mutations.