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Your search keyword '"Dibbens, LM"' showing total 4 results
Start Over Author "Dibbens, LM" Publisher wiley-blackwell
4 results on '"Dibbens, LM"'

1. Mutations in Mammalian Target of Rapamycin Regulator DEPDC5 Cause Focal Epilepsy with Brain Malformations

Author

Scheffer, IE, Heron, SE, Regan, BM, Mandelstam, S, Crompton, DE, Hodgson, BL, Licchetta, L, Provini, F, Bisulli, F, Vadlamudi, L, Gecz, J, Connelly, A, Tinuper, P, Ricos, MG, Berkovic, SF, Dibbens, LM, Scheffer, IE, Heron, SE, Regan, BM, Mandelstam, S, Crompton, DE, Hodgson, BL, Licchetta, L, Provini, F, Bisulli, F, Vadlamudi, L, Gecz, J, Connelly, A, Tinuper, P, Ricos, MG, Berkovic, SF, and Dibbens, LM

Abstract

We recently identified DEPDC5 as the gene for familial focal epilepsy with variable foci and found mutations in >10% of small families with nonlesional focal epilepsy. Here we show that DEPDC5 mutations are associated with both lesional and nonlesional epilepsies, even within the same family. DEPDC5-associated malformations include bottom-of-the-sulcus dysplasia (3 members from 2 families), and focal band heterotopia (1 individual). DEPDC5 negatively regulates the mammalian target of rapamycin (mTOR) pathway, which plays a key role in cell growth. The clinicoradiological phenotypes associated with DEPDC5 mutations share features with the archetypal mTORopathy, tuberous sclerosis, raising the possibility of therapies targeted to this pathway.

Published
2014

2. A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation

Author

Puskarjov, M, Seja, P, Heron, SE, Williams, TC, Ahmad, F, Iona, X, Oliver, KL, Grinton, BE, Vutskits, L, Scheffer, IE, Petrou, S, Blaesse, P, Dibbens, LM, Berkovic, SF, Kaila, K, Puskarjov, M, Seja, P, Heron, SE, Williams, TC, Ahmad, F, Iona, X, Oliver, KL, Grinton, BE, Vutskits, L, Scheffer, IE, Petrou, S, Blaesse, P, Dibbens, LM, Berkovic, SF, and Kaila, K

Abstract

Genetic variation in SLC12A5 which encodes KCC2, the neuron-specific cation-chloride cotransporter that is essential for hyperpolarizing GABAergic signaling and formation of cortical dendritic spines, has not been reported in human disease. Screening of SLC12A5 revealed a co-segregating variant (KCC2-R952H) in an Australian family with febrile seizures. We show that KCC2-R952H reduces neuronal Cl(-) extrusion and has a compromised ability to induce dendritic spines in vivo and in vitro. Biochemical analyses indicate a reduced surface expression of KCC2-R952H which likely contributes to the functional deficits. Our data suggest that KCC2-R952H is a bona fide susceptibility variant for febrile seizures.

Published
2014

3. Investigating genetic variants in microRNA regulators of Neurokinin-1 receptor in sudden infant death syndrome.

Author

Shaukat Z, Byard RW, Vink R, Hussain R, Ricos MG, and Dibbens LM

Subjects
Infant, Humans, Male, Female, Receptors, Neurokinin-1 genetics, Pilot Projects, Polymorphism, Single Nucleotide, Sudden Infant Death genetics, Sudden Infant Death epidemiology, MicroRNAs genetics
Abstract

Sudden infant death syndrome (SIDS) occurs more often in male than in female infants, suggesting involvement of the X-chromosome. Histopathological studies have suggested that altered expression of the Neurokinin-1 receptor may also play a role in the pathogenesis of SIDS. It was hypothesised that genetic variants in three X-chromosome-encoded microRNA (miRNA/miR), known to down-regulate expression of the Neurokinin-1 receptor, may contribute to SIDS., Aim: To identify sequence variants in the miRNAs within a study cohort (27 cases of SIDS and 28 controls) and determine if there was a difference in the frequencies in male and female SIDS infants., Methods: Genomic DNA prepared from stored blood spots was amplified and sequenced to identify genetic variants in miR500A, miR500B and miR320D2., Results: No novel variants in the miRNAs were identified in our study cohort. We identified one known single-nucleotide polymorphism (SNP) in miR320D2: rs5907732 G/T, in both cases and controls. No significant difference in the SNP frequency was observed between male and female SIDS cases., Conclusion: This pilot study suggests that sequence variants in three miRNAs do not contribute to the reported higher prevalence of SIDS in male infants and do not contribute to the pathogenesis of SIDS in our cohort., (© 2022 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Published
2023
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4. BRAT1-associated neurodegeneration: Intra-familial phenotypic differences in siblings.

Author

Smith NJ, Lipsett J, Dibbens LM, and Heron SE

Subjects
Age of Onset, Alleles, Exome, Fatal Outcome, Female, Genes, Recessive, Genetic Loci, Genotype, High-Throughput Nucleotide Sequencing, Humans, Infant, Male, Pedigree, Siblings, Genetic Association Studies, Mutation, Neurodegenerative Diseases diagnosis, Neurodegenerative Diseases genetics, Nuclear Proteins genetics, Phenotype
Abstract

Recessive mutations in BRAT1 cause lethal neonatal rigidity and multifocal seizure syndrome, a phenotype characterized by neonatal microcephaly, hypertonia, and refractory epilepsy with premature death by age 2 years. Recently, attenuated disease variants have been described, suggesting that a wider clinical spectrum of BRAT1-associated neurodegeneration exists than was previously thought. Here, we report two affected siblings with compound heterozygous truncating mutations in BRAT1 and intra-familial phenotypic heterogeneity, with a less severe disease course in the female sibling. This phenotypic variability should be taken into account when treating patients with BRAT1-associated neurodegenerative disease. Mildly affected individuals with BRAT1 mutations show that BRAT1 must be considered as a cause in childhood refractory epilepsy and microcephaly with survival beyond infancy. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Published
2016
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