A missense variant of the ATP1A2 gene is associated with a novel phenotype of progressive sensorineural hearing loss associated with migraine

Oh, Se‐Kyung; Baek, Jeong‐In; Weigand, Karl M.; Venselaar, Hanka; Swarts, H.G.P.; Park, Seong‐Hyun; Raza, Muhammad Hashim; Jung, Da Jung; Choi, Soo‐Young; Lee, Sangheon; Friedrich, Thomas; Vriend, Gert; Koenderink, Jan B.; Kim, Un-Kyung; Lee, Kyu-Yup

doi:10.1038/ejhg.2014.154

Cited by 18 publications

(16 citation statements)

References 38 publications

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“…Furthermore, channels are expressed both in the inner ear and in the brain and could lead to ELH and central auditory dysfunction [Baloh, 1997;Kim et al, 1998;Radtke et al, 2012]. Recently, a variant of ATP1A2 was associated with a new form of hearing loss with migraine in a Korean family [Oh et al, 2015]. Furthermore, the ELH in VM patients had been confirmed by Gürkov et al [2014].…”

Section: Discussionmentioning

confidence: 99%

Audiological Findings in Patients with Vestibular Migraine and Migraine: History of Migraine May Be a Cause of Low-Tone Sudden Sensorineural Hearing Loss

Xue

Lin

et al. 2020

Audiol Neurotol

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Introduction: The aim of this study was to investigate and compare the auditory findings in migraine, vestibular migraine (VM), and healthy controls. Methods: Twenty-eight migraine patients (56 ears), 18 VM (36 ears), and 25 healthy controls (50 ears) were included. Audiometry, speech discrimination scores, distortion product optoacoustic emission (DPOAE), and auditory brainstem response were tested. Results: The pure tone in the VM group showed higher thresholds at lower frequencies (250, 500, 1,000, 2,000 Hz) than the control group, with statistical differences observed (P_{250 Hz} = 0.001, P_{500 Hz} = 0.003, P_{1,000 Hz} = 0.016, P_{2,000 Hz} = 0.002). Compared with the healthy controls, the patients with VM had significantly lower amplitudes of DPOAE at 1 kHz (p < 0.001) and 2 kHz (p = 0.020), and the patients with migraine had lower amplitudes at 2 kHz (p = 0.042). Compared with the control group, the patients with migraine reported prolonged latency of wave V (p = 0.016) and IPL I–V (p = 0.003). The patients with VM had significant prolongation of IPL I–V (p = 0.024). Conclusion: Not only the peripheral, but also the central auditory system was involved in patients with migraine and VM. In particular, lower frequencies of the auditory system were more likely to be involved in VM. The history of migraine may be a cause of low-tone sudden sensorineural hearing loss.

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Section: Discussionmentioning

confidence: 99%

Audiological Findings in Patients with Vestibular Migraine and Migraine: History of Migraine May Be a Cause of Low-Tone Sudden Sensorineural Hearing Loss

Xue

Lin

et al. 2020

Audiol Neurotol

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“…Of note, two ATP1A2 mutations were identified in patients with AHC, such as the I589T mutation reported in an atypical case of AHC (Al-Bulushi et al, 2014 ), and T378M, which was found in two families, either correlated with FHM (Bassi et al, 2004 ) or with AHC (Swoboda et al, 2004 ). Other pathologies associated with ATP1A2 mutations were sensorineural hearing loss (V191M, Oh et al, 2015 ), basilar migraine (R548H, Ambrosini et al, 2005 ), benign familial infantile convulsions (BFIC; R689Q, Vanmolkot et al, 2003 ), generalized epilepsy with febrile seizures (GEFS+; G874S, Costa et al, 2014 ), pulmonary arterial hypertension (S940L, Montani et al, 2013 ) and reversible cerebral vasoconstriction (P979L Hermann et al, 2013 ).…”

Section: Atp1a2 Mutations Correlated With Clinical Migraine Casesmentioning

confidence: 99%

ATP1A2 Mutations in Migraine: Seeing through the Facets of an Ion Pump onto the Neurobiology of Disease

2016

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Mutations in four genes have been identified in familial hemiplegic migraine (FHM), from which CACNA1A (FHM type 1) and SCN1A (FHM type 3) code for neuronal voltage-gated calcium or sodium channels, respectively, while ATP1A2 (FHM type 2) encodes the α2 isoform of the Na+,K+-ATPase's catalytic subunit, thus classifying FHM primarily as an ion channel/ion transporter pathology. FHM type 4 is attributed to mutations in the PRRT2 gene, which encodes a proline-rich transmembrane protein of as yet unknown function. The Na+,K+-ATPase maintains the physiological gradients for Na+ and K+ ions and is, therefore, critical for the activity of ion channels and transporters involved neuronal excitability, neurotransmitter uptake or Ca2+ signaling. Strikingly diverse functional abnormalities have been identified for disease-linked ATP1A2 mutations which frequently lead to changes in the enzyme's voltage-dependent properties, kinetics, or apparent cation affinities, but some mutations are truly deleterious for enzyme function and thus cause full haploinsufficiency. Here, we summarize structural and functional data about the Na+,K+-ATPase available to date and an overview is provided about the particular properties of the α2 isoform that explain its physiological relevance in electrically excitable tissues. In addition, current concepts about the neurobiology of migraine, the correlations between primary brain dysfunction and mechanisms of headache pain generation are described, together with insights gained recently from modeling approaches in computational neuroscience. Then, a survey is given about ATP1A2 mutations implicated in migraine cases as documented in the literature with focus on mutations that were described to completely destroy enzyme function, or lead to misfolded or mistargeted protein in particular model cell lines. We also discuss whether or not there are correlations between these most severe mutational effects and clinical phenotypes. Finally, perspectives for future research on the implications of Na+,K+-ATPase mutations in human pathologies are presented.

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“…Although it was hypothesized that a genetic deficiency in the same region would be related to VM, this genetic deficiency could not actually be demonstrated [69, 70]. Recently, a variant of ATP1A2 was associated with a new form of progressive hearing loss with migraine in a Korean family [71]. …”

Section: Pathogenesis Of Vmmentioning

confidence: 99%

Recent Advances in the Understanding of Vestibular Migraine

Sohn

2016

Behavioural Neurology

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Approximately 1% of the general population and 10% of patients with migraine suffer from vestibular migraine (VM). However, this condition remains relatively unknown; therefore, it is often underdiagnosed despite the recent adoption of international diagnostic criteria for VM. The diagnosis of VM is based on the symptoms, degree, frequency, and duration of the vestibular episodes, a history of migraine, the temporal association of migraine symptoms with vestibular episodes in at least 50% of cases, and the exclusion of other causes. Physical examination and laboratory findings are usually normal in patients with VM but can be used to rule out other vestibular disorders with similar symptoms. The pathophysiology of VM remains incompletely understood; however, several mechanisms link the trigeminal system, which is activated during migraine attacks, and the vestibular system. Because few controlled trials have specifically investigated VM, the treatment options for this order are largely the same as those for migraine and include antiemetics for severe acute attacks, pharmacological migraine prophylaxis, and lifestyle changes.

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A missense variant of the ATP1A2 gene is associated with a novel phenotype of progressive sensorineural hearing loss associated with migraine

Cited by 18 publications

References 38 publications

Audiological Findings in Patients with Vestibular Migraine and Migraine: History of Migraine May Be a Cause of Low-Tone Sudden Sensorineural Hearing Loss

Audiological Findings in Patients with Vestibular Migraine and Migraine: History of Migraine May Be a Cause of Low-Tone Sudden Sensorineural Hearing Loss

ATP1A2 Mutations in Migraine: Seeing through the Facets of an Ion Pump onto the Neurobiology of Disease

Recent Advances in the Understanding of Vestibular Migraine

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