Hedberg Carola, Oldfors Anders, Darin Niklas
Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Pediatrics, University of Gothenburg, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.
Eur J Hum Genet. 2014 May;22(5):707-10. doi: 10.1038/ejhg.2013.223. Epub 2013 Oct 2.
Congenital muscular dystrophies associated with brain malformations are a group of disorders frequently associated with aberrant glycosylation of α-dystroglycan. They include disease entities such a Walker-Warburg syndrome, muscle-eye-brain disease and various other clinical phenotypes. Different genes involved in glycosylation of α-dystroglycan are associated with these dystroglycanopathies. We describe a 5-year-old girl with psychomotor retardation, ataxia, spasticity, muscle weakness and increased serum creatine kinase levels. Immunhistochemistry of skeletal muscle revealed reduced glycosylated α-dystroglycan. Magnetic resonance imaging of the brain at 3.5 years of age showed increased T2 signal from supratentorial and infratentorial white matter, a hypoplastic pons and subcortical cerebellar cysts. By whole exome sequencing, the patient was identified to be compound heterozygous for a one-base duplication and a missense mutation in the gene B3GALNT2 (β-1,3-N-acetylgalactosaminyltransferase 2; B3GalNAc-T2). This patient showed a milder phenotype than previously described patients with mutations in the B3GALNT2 gene.
与脑畸形相关的先天性肌营养不良是一组常与α- dystroglycan糖基化异常相关的疾病。它们包括诸如沃克-沃尔堡综合征、肌肉-眼-脑疾病及各种其他临床表型等疾病实体。参与α- dystroglycan糖基化的不同基因与这些糖基化肌营养不良症相关。我们描述了一名5岁女孩，她有精神运动发育迟缓、共济失调、痉挛、肌肉无力以及血清肌酸激酶水平升高。骨骼肌免疫组织化学显示糖基化α- dystroglycan减少。3.5岁时的脑部磁共振成像显示幕上和幕下白质T2信号增强、脑桥发育不全和皮质下小脑囊肿。通过全外显子组测序，该患者被鉴定为B3GALNT2基因（β-1,3-N-乙酰半乳糖胺基转移酶2；B3GalNAc-T2）存在一个单碱基重复和一个错义突变的复合杂合子。该患者表现出比先前描述的B3GALNT2基因突变患者更轻的表型。
