A homozygous nonsense mutation in the Fukutin gene causes a Walker-Warburg syndrome phenotype

Bernabe, D. Beltran Valero de; Bokhoven, Hans van; Beusekom, Ellen van; Akker, Wouter van den; Kant, Sarina G.; Dobyns, William B.; Cormand, Bru; Currier, Sophie; Hamel, B.C.J.; Talim, Beril; Topaloǧlu, Haluk; Brunner, Han G.

doi:10.1136/jmg.40.11.845

Cited by 138 publications

(46 citation statements)

References 12 publications

(9 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Once compound heterozygotes were identified, the clinical spectrum was expanded to include ocular defects and a poorer prognosis, 24 and homozygous nonsense mutations were shown to yield WWS. 25 Likewise, mutations in POMT1 were originally reported only to give rise to WWS, which presents with the most severe clinical features of all the dystroglycanopathies (the average life expectancy of WWS patients is 0.8 years). 2 A recent report, however, identified a POMT1 mutation (A200P) as causing a far milder limb-girdle muscular dystrophy with mental retardation (LGMD2K).…”

Section: The Dystroglycanopathies: Clinical and Genetic Findingsmentioning

confidence: 99%

Mechanisms of Disease: congenital muscular dystrophies—glycosylation takes center stage

Martin

2006

Nat Rev Neurol

View full text Add to dashboard Cite

SUMMARYRecent studies have defined a group of muscular dystrophies, now termed the dystroglycanopathies, as novel disorders of glycosylation. These conditions include Walker-Warburg syndrome, muscleeye-brain disease, Fukuyama-type congenital muscular dystrophy, congenital muscular dystrophy types 1C and 1D, and limb-girdle muscular dystrophy type 2I. Although clinical findings can be highly variable, dystroglycanopathies are all characterized by cortical malformations and ocular defects at the more severe end of the clinical spectrum, in addition to muscular dystrophy. All of these disorders are defined by the underglycosylation of α-dystroglycan. Defective glycosylation of dystroglycan severs the link between this important cell adhesion molecule and the extracellular matrix, thereby contributing to cellular pathology. Recent experiments indicate that glycosylation might not only define forms of muscular dystrophy but also provide an avenue to the development of therapies for these disorders.

show abstract

Section: The Dystroglycanopathies: Clinical and Genetic Findingsmentioning

confidence: 99%

Mechanisms of Disease: congenital muscular dystrophies—glycosylation takes center stage

Martin

2006

Nat Rev Neurol

View full text Add to dashboard Cite

show abstract

“…Moreover, a number of neurodevelopmental disorders are associated specifically with hypoplasia or agenesis of the vermis including Joubert [1,2,3], Walker-Warburg [4], Meckel-Gruber [5], and Smith-Lemli-Opitz [6] syndromes. Reduced vermis size has also been observed in children with autism spectrum disorders [7] as well as Fragile X syndrome [8].…”

Section: Introductionmentioning

confidence: 99%

Neuronal Migration Defect of the Developing Cerebellar Vermis in Substrains of C57BL/6 Mice: Cytoarchitecture and Prevalence of Molecular Layer Heterotopia

Mangaru

Salem²,

Sherman³

et al. 2013

Dev Neurosci

View full text Add to dashboard Cite

Abnormal development of the cerebellum is often associated with disorders of movement, postural control, and motor learning. Rodent models are widely used to study normal and abnormal cerebellar development and have revealed the roles of many important genetic and environmental factors. In the present report we describe the prevalence and cytoarchitecture of molecular-layer heterotopia, a malformation of neuronal migration, in the cerebellar vermis of C57BL/6 mice and closely-related strains. In particular, we found a diverse number of cell-types affected by these malformations including Purkinje cells, granule cells, inhibitory interneurons (GABAergic and glycinergic), and glia. Heterotopia were not observed in a sample of wild-derived mice, outbred mice, or inbred mice not closely related to C57BL/6 mice. These data are relevant to the use of C57BL/6 mice as models in the study of brain and behavior relationships and provide greater understanding of human cerebellar dysplasia.

show abstract

“…This was thought to explain why FCMD is much less common outside of the Japanese population. In fact, although fukutin mutations have been described in a number of non-Japanese patients, some present with a much milder form of dystroglycanopathy that does not involve the CNS [33], while others have the more severe WWS [24,34].…”

Section: The Dystroglycanopathiesmentioning

confidence: 96%

“…The disease shows extensive genetic heterogeneity [21], with causal mutations identified in the O-mannosyltransferases POMT1 and POMT2 [22,23], and the putative glycosyltransferases fukutin [24], FKRP [25] and LARGE [26]. Based on genetic analysis of families, there are several additional genetic loci for this syndrome [21].…”

Section: The Dystroglycanopathiesmentioning

confidence: 98%

Dystroglycan glycosylation and muscular dystrophy

Moore

Hewitt

2008

Glycoconj J

View full text Add to dashboard Cite

Dystroglycan is an integral member of the skeletal muscle dystrophin glycoprotein complex, which links dystrophin to proteins in the extracellular matrix. Recently, a group of human muscular dystrophy disorders have been demonstrated to result from defective glycosylation of the alpha-dystroglycan subunit. Genetic studies of these diseases have identified six genes that encode proteins required for the synthesis of essential carbohydrate structures on dystroglycan. Here we highlight their known or postulated functions. This glycosylation pathway appears to be highly specific (dystroglycan is the only substrate identified thus far) and to be highly conserved during evolution.

show abstract

A homozygous nonsense mutation in the Fukutin gene causes a Walker-Warburg syndrome phenotype

Cited by 138 publications

References 12 publications

Mechanisms of Disease: congenital muscular dystrophies—glycosylation takes center stage

Mechanisms of Disease: congenital muscular dystrophies—glycosylation takes center stage

Neuronal Migration Defect of the Developing Cerebellar Vermis in Substrains of C57BL/6 Mice: Cytoarchitecture and Prevalence of Molecular Layer Heterotopia

Dystroglycan glycosylation and muscular dystrophy

Contact Info

Product

Resources

About