Tomoko Yamamoto

By Tomoko Yamamoto, Yoichiro Kato and Noriyuki Shibata

Fukuyama congenital muscular dystrophy (FCMD) is one of the congenital muscular dystrophies, showing central nervous system (CNS) and ocular lesions, in addition to muscular dystrophy. It is included in α-dystroglycanopathy, an entity of muscular dystrophies caused by reduced glycosylation of α-dystroglycan (α-DG). Studies of ocular lesions are not so many, compared with those of the muscle and CNS. Clinical ocular manifestations are myopia, strabismus, retinal detachment, and so on. Since the retina has a structure partly resembling the cerebral cortex, pathological findings similar to those found in the brain have been reported. The major observation considered to be involved in the pathogenesis of retinal lesions is abnormalities in the internal limiting membrane formed by Müller cells, which is corresponding to the glia limitans formed by astrocytes in the brain. Fukutin, responsible for FCMD, and α-DG are expressed in Müller cells. Moreover, fukutin may be involved in synaptic functions of retinal neurons through the glycosylation of α-DG. In this chapter, ocular lesions of fetal and child FCMD patients are presented, especially focusing on pathological findings of the retina, and functions of fukutin are discussed.

Part of the book: Muscular Dystrophies

By Tomoko Yamamoto, Yukinori Okamura, Ryota Tsukui, Yoichiro Kato, Hiromi Onizuka and Kenta Masui

Fukuyama congenital muscular dystrophy (FCMD), accompanying central nervous system (CNS) and ocular anomalies, is the second common muscular dystrophy in Japan, and the responsible gene is fukutin. The lesions are mainly caused by fragile basement membrane/cell membrane due to hypoglycosylation of α-dystroglycan (α-DG), and astrocytes play a crucial role for CNS malformation. On the other hand, since fukutin is expressed almost ubiquitously, diverse functions of fukutin, besides the glycosylation of α-DG, can be considered. As for the CNS, fukutin possibly upregulates cyclin D1 expression as a cofactor of activator protein-1 in astrocytoma. Moreover, fukutin may be involved in the phosphorylation of tau, one of the key proteins of dementia represented by Alzheimer’s disease, in glutamatergic neurons. A presynaptic function in GABAergic neurons is also suggested. Owing to the recent advances of molecular and biochemical techniques, new therapeutic strategies are under consideration, even for brain malformation, which begins to be formed during the first trimester in utero. Recovery of hypoglycosylation of α-DG supposed to be a main therapeutic target, but to know various functions and regulation systems of fukutin might be important for developing suitable therapies.

Part of the book: Potential Therapeutic Strategies for Muscular Dystrophy