Dennis Lal, PhD

  • Genomic Medicine Institute
  • Lerner Research Institute
  • 9500 Euclid Avenue
  • Cleveland, Ohio 44195
  • lald@ccf.org
  • Phone: (216) 444-6701

Dr. Lal uses genetic data from in-house and globally collected patient cohorts to discover genes related to epilepsy syndromes, to develop novel methods for interpreting missense variants and to characterize patient disease trajectories. Through his research, Dr. Lal hopes to increase our understanding of how alterations in the genome contribute to neurodevelopmental disorders and, ultimately, to improve patient outcomes.

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Epilepsy Disease Gene Discovery

Lal D, Reinthaler EM, Schubert J, et al. DEPDC5 mutations in genetic focal epilepsies of childhood. Ann Neurol. 2014 May;75(5):788-92. doi: 10.1002/ana.24127. PMID: 24591017

 

Lemke JR*, Lal D*, Reinthaler EM, Steiner I, et al. Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes. Nat Genet. 2013 Sep;45(9):1067-72. doi: 10.1038/ng.2728. PMID: 23933819

 

Reinthaler EM*, Dejanovic B*, Lal D*, et al. Rare variants in γ-aminobutyric acid type A receptor genes in rolandic epilepsy and related syndromes. Ann Neurol.2015 Jun;77(6):972-86. doi: 10.1002/ana.24395 PMID: 25726841

 

Epilepsy Copy Number Risk Allele Discovery

Dejanovic B*, Lal D*, Catarino CB, et al. Exonic microdeletions of the gephyrin gene impair GABAergic synaptic inhibition in patients with idiopathic generalized epilepsy. Neurobiol Dis. 2014 Jul;67:88-96. doi: 10.1016/j.nbd.2014.02.001. PMID: 24561070

 

Lal D, Ruppert AK, Trucks H, et al. Burden analysis of rare microdeletions suggests a strong impact of neurodevelopmental genes in genetic generalised epilepsies. PLoS Genet. 2015 May 7;11(5):e1005226. doi: 10.1371/journal.pgen.1005226. PMID: 25950944

 

Pérez-Palma E, Helbig I, Klein KM, … , Perucca E, Zara F, Weber YG, Lal D. Heterogeneous Contribution of Microdeletions in the Development of Common Generalized and Focal epilepsies. J Med Genet. 2017 Jul 29. pii: jmedgenet-2016-104495. doi: 10.1136/jmedgenet-2016-104495. PubMed PMID: 28756411

 

Reinthaler EM*, Lal D*, Lebon S, et al. 16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy. Hum Mol Genet. 2014 Nov 15;23(22):6069-80. doi: 10.1093/hmg/ddu306. PMID: 24939913

 

Genetics of Neurodevelopmental Disorders

Hardies K, de Kovel CG, Weckhuysen S, … , Lal D, et al. Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia. Brain. 2015 Nov;138(Pt 11):3238-50. doi: 10.1093/brain/awv263. PMID: 26384929


Lal D, Becker K, Motameny S, et al. Homozygous missense mutation of NDUFV1 as the cause of infantile bilateral striatal necrosis. Neurogenetics. 2013 Feb;14(1):85-7. doi: 10.1007/s10048-013-0355-z. PMID: 23334465


Lal D, Neubauer BA, Toliat MR, et al. Increased Probability of Co-Occurrence of Two Rare Diseases in Consanguineous Families and Resolution of a Complex Phenotype by Next Generation Sequencing. PLoS One. 2016 Jan 20;11(1):e0146040. doi: 10.1371/journal.pone.0146040 PMID: 26789268

 

Interpretation and Translation of Genetic Variants

Lal D, May P, Samocha K, et al. Gene family information facilitates variant interpretation and identification of disease-associated genes. BioRxiv 2017; doi: https://doi.org/10.1101/159780


Lal D, Reinthaler EM, Dejanovic B, et al. Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes. PLoS One. 2016 Mar 18;11(3):e0150426. doi: 10.1371/journal.pone.0150426. PubMed PMID: 26990884

 

Lemke JR, Geider K, Helbig KL, … , Lal D, et al. Delineating the GRIN1 phenotypic spectrum: A distinct genetic NMDA receptor encephalopathy. Neurology. 2016 Jun 7;86(23):2171-8. doi: 10.1212/WNL.0000000000002740. PMID: 27164704; PubMed Central PMCID: PMC4898312

 

Neupert LM, Nothnagel M, May P, Palotie A, Daly M, Nürnberg P, Blümcke I, Lal D. Reassessment of Lesion-Associated Gene and Variant Pathogenicity in Focal Human Epilepsies. BioRxiv 2017; doi: https://doi.org/10.1101/130203