DPM2-CDG: A muscular dystrophy-dystroglycanopathy syndrome with severe epilepsy

被引：98

作者：

Barone, Rita ^{[2
]}

Aiello, Chiara ^{[3
]}

Race, Valerie ^{[4
]}

Morava, Eva ^{[5
]}

Foulquier, Francois ^{[6
]}

Riemersma, Moniek ^{[7
]}

Passarelli, Chiara ^{[3
]}

Concolino, Daniela ^{[8
]}

Carella, Massimo ^{[9
]}

Santorelli, Filippo ^{[10
]}

Vleugels, Wendy ^{[4
]}

Mercuri, Eugenio ^{[11
]}

Garozzo, Domenico ^{[12
]}

Sturiale, Luisa ^{[12
]}

Messina, Sonia ^{[8
]}

Jaeken, Jaak ^{[13
]}

Fiumara, Agata ^{[2
]}

Wevers, Ron A. ^{[14
]}

Bertini, Enrico ^{[3
]}

Matthijs, Gert ^{[4
]}

Lefeber, Dirk J. ^{[1
,2
,5
,14
]}

机构：

[1] Radboud Univ Nijmegen, Dept Neurol, Inst Genet & Metab Dis, Med Ctr, NL-6525 GA Nijmegen, Netherlands

[2] Univ Catania, Dept Pediat, Catania, Italy

[3] Bambino Gesu Childrens Res Hosp, Mol Med Lab, Rome, Italy

[4] Univ Leuven, Ctr Human Genet, Louvain, Belgium

[5] Radboud Univ Nijmegen, Dept Pediat, Med Ctr, NL-6525 GA Nijmegen, Netherlands

[6] Lille Univ Sci & Technol, Struct & Funct Glycobiol Unit, CNRS, IFR147,UMR 8576, Villeneuve Dascq, France

[7] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, NL-6525 GA Nijmegen, Netherlands

[8] Magna Graecia Univ Catanzaro, Dept Pediat, Catanzaro, Italy

[9] Casa Sollievo Sofferenza Hosp, IRCCS, San Giovanni Rotondo, Italy

[10] IRCCS, Stella Maris Inst, Pisa, Italy

[11] Univ Cattolica Sacro Cuore, Dept Pediat Neurol, I-00168 Rome, Italy

[12] CNR, Inst Chem & Technol Polymers, Catania, Italy

[13] Katholieke Univ Leuven Hosp, Dept Pediat, Ctr Metab Dis, Louvain, Belgium

[14] Radboud Univ Nijmegen, Lab Genet Endocrine & Metab Dis, Med Ctr, NL-6525 GA Nijmegen, Netherlands

来源：

ANNALS OF NEUROLOGY | 2012年 / 72卷 / 04期

关键词：

DOLICHOL-PHOSPHATE-MANNOSE; CAUSES CONGENITAL DISORDER; GLYCOSYLATION; SYNTHASE; BIOSYNTHESIS; GENE; DPM1;

D O I：

10.1002/ana.23632

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective: Congenital disorders of glycosylation (CDG) are a group of metabolic diseases due to defects in protein and lipid glycosylation. We searched for the primary defect in 3 children from 2 families with a severe neurological phenotype, including profound developmental delay, intractable epilepsy, progressive microcephaly, severe hypotonia with elevated blood creatine kinase levels, and early fatal outcome. There was clinical evidence of a muscular dystrophydystroglycanopathy syndrome, supported by deficient O-mannosylation by muscle immunohistochemistry. Methods: Biochemical and molecular methods were combined to pinpoint the defect in the glycosylation pathway in the endoplasmic reticulum. Results: Metabolic investigations revealed CDG-I, pointing to a defect in protein N-glycosylation in the endoplasmic reticulum. Analysis of lipid-linked oligosaccharides in fibroblasts showed accumulation of Dol-PP-GlcNAc(2)-Man(5). DNA analysis revealed mutations in DPM2, 1 of the subunits of the dolichol-phosphate-mannose (DPM) synthase; the patient in the first family is compound heterozygous for 2 mutations (c.68A>G, predicting a missense mutation p.Y23C and c.4-1G>C, a splice mutation), whereas the patients in the second family are homozygous for the same missense mutation (c.68A>G, p.Y23C). Interpretation: We describe a new CDG, due to a deficiency of DPM2. Hence, mutations have now been described in the genes for the 3 subunits of DPM: DPM1, DPM2, and DPM3, whereby DPM2-CDG links the congenital disorders of glycosylation to the congenital muscular dystrophies. ANN NEUROL 2012;72:550558

引用

页码：550 / 558

页数：9

共 25 条

[1] DPM1, the catalytic subunit of dolichol-phosphate mannose synthase, is tethered to and stabilized on the endoplasmic reticulum membrane by DPM3 [J].