Pial-glial barrier abnormalities in fetuses with Fukuyama congenital muscular dystrophy

A POGLUT1 mutation causes a muscular dystrophy with reduced notch signaling and satellite cell loss

“…Moreover, in skin fibroblasts from patients, the level of both functional a-dystroglycan glycosylation, examined by Western blot and flow cytometry (Stevens et al, 2013b), and its ability to bind laminin ( Fig 2B and Appendix Fig S5B) were normal, unlike known secondary dystroglycanopathies, which usually result in decreased functional a-dystroglycan glycosylation in both muscle and the skin fibroblasts (Willer et al, 2012;Carss et al, 2013;Stevens et al, 2013a). Finally, although basement membrane defects are commonly observed in dystroglycanopathies (Yamamoto et al, 1997;Goddeeris et al, 2013), transmission electron microscopy showed normal muscle ultrastructure in patients, with no alterations in basement membrane compaction (Fig 2C and Appendix Fig S5C). A The family pedigree, where circles denote female members, squares male members, solid symbols affected members, and white symbols asymptomatic members with normal physical exam; the dots indicate heterozygous carriers, and double line denotes a consanguineous marriage.…”

Cellular and Axonal Constituents of Neocortical Molecular Layer Heterotopia

“…These diverse disorders surprisingly share one important neuroanatomical phenotype in common. Specifically, postmortem analyses of individuals affected by these disorders have revealed the presence of neocortical heterotopia consisting of aggregations of hundreds of neurons and glia in the molecular layer (layer I) that are indicative of neuronal migration defect [1,2,3,4,5,6,7,8]. Despite the potential clinical importance of understanding how heterotopia affect neocortical function in such disparate disorders, much remains to be revealed regarding the anatomy, physiology and etiology of heterotopia.…”

Possible Diverse Roles of Fukutin: More Than Basement Membrane Formation?

“…Morphological abnormalities of the basement membrane and the glia limitans have been reported in the CNS of FCMD (Fig. 2) (Nakano et al 1996;Takada et al 1987;Yamamoto et al 1997;Yamamoto et al 2010) and WWS (Beltrán-Valero de Bernabé 2002;Miller et al 1991) patients and in mouse models of FCMD (Chiyonobu et al 2005) and MEB (Yang et al 2007). Fragile basement membrane caused by hypoglycosylation GL: glia limitans, CP: cortical plate, WM: white matter, GM: germinal matrix, EP: ependymal cells, BM: basement membrane, As: endfeet of astrocytes Fig.…”

“…In fetal cases, the glia limitans formed by astrocytic endfeet in the CNS surface is disrupted, through which the glioneuronal tissues over-migrate into the leptomeninges (Fig. 2) (Nakano et al 1996;Takada et al 1987;Yamamoto et al 1997;Yamamoto et al 2010). Even in non-disrupted areas, both cell and basement membranes are abnormal, electron microscopically (Yamamoto et al 1997;Yamamoto et al 2010).…”

“…2) (Nakano et al 1996;Takada et al 1987;Yamamoto et al 1997;Yamamoto et al 2010). Even in non-disrupted areas, both cell and basement membranes are abnormal, electron microscopically (Yamamoto et al 1997;Yamamoto et al 2010). The degree of disruption varies from case to case and even from area to area in a single patient (Takada et al 1987;Yamamoto et al 1997).…”