Epilepsy, status epilepticus, and hemiplegic migraine coexisting with a novel SLC4A4 mutation

Gil-Perotín, Sara; Jaijo, Teresa; Verdú, Andrés G; Rubio, Pilar; Mazón, Miguel; Gasqué-Rubio, Raquel; Díaz, Samuel

doi:10.1007/s10072-020-04961-x

Cited by 10 publications

(3 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, we demonstrate that LMTK3 copurifies from the brain with KCC2, the principal mediator of Cl − extrusion employed by mature neurons, and its activity is a prerequisite for fast inhibitory neurotransmission mediated by GABA A Rs. Immunopurification coupled with quantitative mass spectroscopy revealed that LMTK3 and KCC2 exist as stable protein complexes in brain plasma membrane in an approximate stoichiometry of 2:1—stoichiometric levels of myo18, an unconventional myosin, that regulates vesicular trafficking 49 and the electrogenic Na/bicarbonate transporter SLC4A4, an epilepsy risk gene 50 copurified with LMTK3. Notably in addition to Cl − , GABA A R receptors are also permeable to bicarbonate, 51 thus, the proximity of KCC2 and SLC4A4 may allow neurons to fine-tune the polarity of GABA A R currents.…”

Section: Discussionmentioning

confidence: 99%

The brain-specific kinase LMTK3 regulates neuronal excitability by decreasing KCC2-dependent neuronal Cl− extrusion

Cho,

Kontou,

Smalley

et al. 2024

iScience

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

The brain-specific kinase LMTK3 regulates neuronal excitability by decreasing KCC2-dependent neuronal Cl− extrusion

Cho,

Kontou,

Smalley

et al. 2024

iScience

View full text Add to dashboard Cite

“…The SLC4A4 gene has recently been identified as the source of a condition characterized by metabolic acidosis due to renal failure to acidify urine. This disorder is caused by an abnormal function of the sodium and bicarbonate cotransporter encoded by the gene NBCe1 [ 11 ]. Expression of NBCe1 in other organs, such as the CNS, can cause extrarenal symptoms associated with the SLC4A4 mutation.…”

Section: Discussionmentioning

confidence: 99%

Unusual Presentation of a Hemiplegic Migraine in a Seven-Year-Old Child: A Case Report

Alebaji¹,

Ani²,

Rozieh³

et al. 2023

Cureus

View full text Add to dashboard Cite

In the pediatric population, headache is a common presenting symptom, and migraine is often the diagnosis. A hemiplegic migraine is characterized by an aura and sudden-onset weakness on one side of the body that usually resolves without causing any permanent neurological damage. In this case, we present a seven-yearold male child with a known case of proximal tubular dysfunction (homozygous mutation in the SLC4A4 gene) who presented to the emergency department with a one-day history of weakness on the right side of his body. A few hours after being discharged from the hospital, he began complaining of a severe headache on the left side, accompanied by photophobia, phonophobia, and high fever. Radiology scans and laboratory workup were unremarkable, and encephalitis was ruled out. He was later diagnosed with hemiplegic migraine based on his history and clinical presentation.

show abstract

“…Until now, WES was typically applied to cohorts of patients with HM, testing several hundred cases in an attempt to either find causal mutations in known HM genes or novel HM genes patients that are negative for mutations in CACNA1A, ATP1A2, and SCN1A. Until now results have not led to additional (undisputed) HM genes (9)(10)(11)51,52). This may indicate that HM in mutation-negative patients may be oligogenic or polygenic, in line with the excess presence of common variants in such patients (12).…”

Section: Exome and Genome Sequencing In Migrainementioning

confidence: 99%

Migraine genetics: Status and road forward

et al. 2023

View full text Add to dashboard Cite

Background Migraine is considered a multifactorial genetic disorder. Different platforms and methods are used to unravel the genetic basis of migraine. Initially, linkage analysis in multigenerational families followed by Sanger sequencing of protein-coding parts (exons) of genes in the genomic region shared by affected family members identified high-effect risk DNA mutations for rare Mendelian forms of migraine, foremost hemiplegic migraine. More recently, genome-wide association studies testing millions of DNA variants in large groups of patients and controls have proven successful in identifying many dozens of low-effect risk DNA variants for the more common forms of migraine with the number of associated DNA variants increasing steadily with larger sample sizes. Currently, next-generation sequencing, utilising whole exome and whole genome sequence data, and other omics data are being used to facilitate their functional interpretation and the discovery of additional risk factors. Various methods and analysis tools, such as genetic correlation and causality analysis, are used to further characterise genetic risk factors. Findings We describe recent findings in genome-wide association studies and next-generation sequencing analysis in migraine. We show that the combined results of the two most recent and most powerful migraine genome-wide association studies have identified a total of 178 LD-independent ( r2 < 0.1) genome-wide significant single nucleotide polymorphisms (SNPs), of which 99 were unique to Hautakangas et al., 11 were unique to Choquet et al., and 68 were identified by both studies. When considering that Choquet et al. also identified three SNPs in a female-specific genome-wide association studies then these two recent studies identified 181 independent SNPs robustly associated with migraine. Cross-trait and causal analyses are beginning to identify and characterise specific biological factors that contribute to migraine risk and its comorbid conditions. Conclusion This review provides a timely update and overview of recent genetic findings in migraine.

show abstract

Epilepsy, status epilepticus, and hemiplegic migraine coexisting with a novel SLC4A4 mutation

Cited by 10 publications

References 20 publications

The brain-specific kinase LMTK3 regulates neuronal excitability by decreasing KCC2-dependent neuronal Cl− extrusion

The brain-specific kinase LMTK3 regulates neuronal excitability by decreasing KCC2-dependent neuronal Cl− extrusion

Unusual Presentation of a Hemiplegic Migraine in a Seven-Year-Old Child: A Case Report

Migraine genetics: Status and road forward

Contact Info

Product

Resources

About