Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker-Warburg syndrome

Bernabe, D. Beltran Valero de; Voït, Thomas; Longman, Cheryl; Steinbrecher, Alice; Straub, Volker; Yuva, Yeliz; Herrmann, Ralf; Sperner, J; Korenke, Christoph; Diesen, Charlotta; Dobyns, William B.; Brunner, Han G.; Bokhoven, Hans van; Brockington, M; Muntoni, Francesco

doi:10.1136/jmg.2003.013870

Cited by 246 publications

(160 citation statements)

References 36 publications

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“…12 It is the main CNS feature of CMDs with O-glycosylation defects of ␣-dystroglycan, even though it is difficult to differentiate the genetic causes on the basis of brain MRI because of overlapping phenotypes. [19][20][21][22][23] Cerebral, cerebellar, and brainstem abnormalities have been well documented in the major phenotypes: FCMD, WWS, and MEB. WWS displays severe cerebral cortical dysplasia, hypomyelination, dysplastic tectum, pontomedullary kink, severe hypoplasia of the vermis, and dysplastic cerebellar hemispheres.…”

Section: Resultsmentioning

confidence: 99%

Midbrain–hindbrain involvement in lissencephalies

Jissendi-Tchofo¹,

Kara²,

Barkovich³

2009

Neurology

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Objectives:To determine the involvement of the midbrain and hindbrain (MHB) in the groups of classic (cLIS), variant (vLIS), and cobblestone complex (CBSC) lissencephalies and to determine whether a correlation exists between the cerebral malformation and the MHB abnormalities.Methods: MRI scans of 111 patients (aged 1 day to 32 years; mean 5 years 4 months) were retrospectively reviewed. After reviewing the brain involvement on MRI, the cases were reclassified according to known mutation (LIS1, DCX, ARX, VLDLR, RELN, MEB, WWS) or mutation phenotype (LIS1-P, DCX-P, RELN-P, ARX-P, VLDLR-P) determined on the basis of characteristic MRI features. Abnormalities in the MHB were then recorded. For each structure, a score was assigned, ranging from 0 (normal) to 3 (severely abnormal). The differences between defined groups and the correlation between the extent of brain agyria/pachygyria and MHB involvement were assessed using Kruskal-Wallis and 2 McNemar tests. Results:There was a significant difference in MHB appearance among the three major groups of cLIS, vLIS, and CBSC. The overall score showed a severity gradient of MHB involvement: cLIS (0 or 1), vLIS (7), and CBSC (11 or 12). The extent of cerebral lissencephaly was significantly correlated with the severity of MHB abnormalities (p ϭ 0.0029). Conclusion: GLOSSARYA ϭ autosomal; ACC ϭ agenesis of corpus callosum; AD ϭ autosomal dominant; AP ϭ anteroposterior; AR ϭ autosomal recessive; CBL ϭ cerebellar; CBSC ϭ cobblestone complex; cLIS ϭ classic lissencephaly; CMD ϭ congenital muscular dystrophy; CSZ ϭ cell-sparse zone; DV ϭ dorsal-ventral; FCMD ϭ Fukuyama congenital muscular dystrophy; IVH ϭ inferior vermis hypoplasia; LV ϭ lateral ventricle; m ϭ medulla; M ϭ midbrain; MDS ϭ Miller-Dieker syndrome; MEB ϭ muscle-eyebrain; MHB ϭ midbrain and hindbrain; MR ϭ magnetic resonance; ND ϭ not determined; P ϭ pons; RC ϭ rostrocaudal; SCBH ϭ subcortical band heterotopia; SELH ϭ subependymal linear heterotopia; V ϭ vermis; vLIS ϭ variant lissencephaly; WI ϭ weighted image; WWS ϭ Walker-Warburg syndrome; XLD ϭ X-linked dominant; XLR ϭ X-linked recessive.The term lissencephaly (smooth outer brain surface) refers to a paucity of gyral and sulcal development. 1 It encompasses a spectrum of gyral malformations ranging from complete agyria to regional pachygyria and includes subcortical band heterotopia. Lissencephaly has been traditionally classified in two distinct groups: classic (cLIS, formerly called lissencephaly type 1) and cobblestone complex (CBSC, formerly called lissencephaly type 2) based on both brain imaging and pathology. To date, five genes have been identified as causing or contributing to human cLIS: LIS1, 14-3-3 in Miller-Dieker syndrome (MDS), DCX, RELN, and ARX. [1][2][3][4][5][6] A new classification has recently been proposed defining four groups of cLIS differing from each other by genetics and neuropathologic features of the cerebral cortex, cerebellum, and brainstem. 3 1)

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Section: Resultsmentioning

confidence: 99%

Midbrain–hindbrain involvement in lissencephalies

Jissendi-Tchofo¹,

Kara²,

Barkovich³

2009

Neurology

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“…In all MDC1C cases investigated, staining ␣-dystroglycan by VIA4-1 and/or IIH6 monoclonal antibodies was abnormal, and staining of laminin ␣ 2 -chain was decreased, whereas the LGMD2I cases studied showed a variable decreases in VIA4-1 and/or IIH6 staining and often (but not always) a laminin ␣ 2 -chain deficiency was found (163,167,170 ). Diagnosis: As the function of FKRP is unknown at present, the diagnosis can be confirmed only at the molecular genetic level (163,167,169 ).…”

Section: Laboratory Findingsmentioning

confidence: 99%

Mechanisms in Protein O-Glycan Biosynthesis and Clinical and Molecular Aspects of Protein O-Glycan Biosynthesis Defects: A Review

et al. 2006

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Background: Genetic diseases that affect the biosynthesis of protein O-glycans are a rapidly growing group of disorders. Because this group of disorders does not have a collective name, it is difficult to get an overview of O-glycosylation in relation to human health and disease. Many patients with an unsolved defect in Nglycosylation are found to have an abnormal O-glycosylation as well. It is becoming increasingly evident that the primary defect of these disorders is not necessarily localized in one of the glycan-specific transferases, but can likewise be found in the biosynthesis of nucleotide sugars, their transport to the endoplasmic reticulum (ER)/Golgi, and in Golgi trafficking. Already, disorders in O-glycan biosynthesis form a substantial group of genetic diseases. In view of the number of genes involved in O-glycosylation processes and the increasing scientific interest in congenital disorders of glycosylation, it is expected that the number of identified diseases in this group will grow rapidly over the coming years. Content: We first discuss the biosynthesis of protein O-glycans from their building blocks to their secretion from the Golgi. Subsequently, we review 24 different genetic disorders in O-glycosylation and 10 different genetic disorders that affect both N-and O-glycosylation. The key clinical, metabolic, chemical, diagnostic, and genetic features are described. Additionally, we describe methods that can be used in clinical laboratory screening for protein O-glycosylation biosynthesis defects and their

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“…When MRIs of affected patients began to be performed, they showed cerebral cortical dysgenesis, abnormalities of myelination, and marked disturbances of brain stem and cerebellar development (Van der Knaap et al 1997;Barkovich 1998). The brain, muscle, and ocular anomalies all result from abnormal linkage of basement membrane to muscle cells or (in the brain and eye) radial glia transporting migrating cells (de Bernabe et al 2003;Beltran-Valero de Bernabe 2004;van Reeuwijk et al 2005van Reeuwijk et al , 2006van Reeuwijk et al , 2007van Reeuwijk et al , 2010. As the linkages seemed to depend on glycosylation of a-dystroglycan (a-DG) on the muscle fibers/radial glial endfeet, these disorders became known as dystroglycanopathies (Martin 2005), although the term "cobblestone malformation" is currently preferred.…”

Section: Cobblestone Malformationsmentioning

confidence: 99%

Malformations of Cortical Development and Epilepsy

Barkovich

Dobyns²,

Guerrini

2015

Cold Spring Harbor Perspectives in Medicine

113

108

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Malformations of cortical development (MCDs) are an important cause of epilepsy and an extremely interesting group of disorders from the perspective of brain development and its perturbations. Many new MCDs have been described in recent years as a result of improvements in imaging, genetic testing, and understanding of the effects of mutations on the ability of their protein products to correctly function within the molecular pathways by which the brain functions. In this review, most of the major MCDs are reviewed from a clinical, embryological, and genetic perspective. The most recent literature regarding clinical diagnosis, mechanisms of development, and future paths of research are discussed.

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Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker-Warburg syndrome

Cited by 246 publications

References 36 publications

Midbrain–hindbrain involvement in lissencephalies

Midbrain–hindbrain involvement in lissencephalies

Mechanisms in Protein O-Glycan Biosynthesis and Clinical and Molecular Aspects of Protein O-Glycan Biosynthesis Defects: A Review

Malformations of Cortical Development and Epilepsy

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