<i>FGF14</i>‐related episodic ataxia: delineating the phenotype of Episodic Ataxia type 9

Piarroux, Julie; Riant, Florence; Humbertclaude, Véronique; Remerand, Ganaëlle; Hadjadj, Jessica; Rejou, F; Coubes, Christine; Pinson, Lucile; Meyer, Pierre; Roubertie, Agathe

doi:10.1002/acn3.51005

Cited by 36 publications

(35 citation statements)

References 18 publications

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“…Most of the patients suffer from additional neurological symptoms, such as epilepsy, dystonia, and migraine‐like headache. Based on such additional neurological symptoms as well as on genetic origin nine variants of autosomal dominant EAs (EA1 to 9) have been distinguished (Cader, Steckley, Dyment, McLachlan, & Ebers, 2005; Conroy et al, 2014; Damji et al, 1996; Kerber, Jen, Lee, Nelson, & Baloh, 2007; Ophoff et al, 1996; Piarroux et al, 2020). EA1 and EA2 are the most common and best characterized forms of episodic ataxia.…”

Section: Introductionmentioning

confidence: 99%

Functional consequences of SLC1A3 mutations associated with episodic ataxia 6

et al. 2020

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The episodic ataxias (EA) are a group of inherited neurological diseases characterized by paroxysmal cerebellar incoordination. There exist nine forms of episodic ataxia with distinct neurological symptoms and genetic origins. Episodic ataxia type 6 (EA6) differs from other EA forms in long attack duration, epilepsy and absent myokymia, nystagmus, and tinnitus. It has been described in seven families, and mutations in SLC1A3, the gene encoding the glial glutamate transporter EAAT1, were reported in each family. How these mutations affect EAAT1 expression, subcellular localization, and function, and how such alterations result in the complex neurological phenotype of EA6 is insufficiently understood. We here compare the functional consequences of all currently known mutations by heterologous expression in mammalian cells, biochemistry, confocal imaging, and whole-cell patch clamp recordings of EAAT1 transport and anion currents. We observed impairments of multiple EAAT1 properties ranging from changes in transport function, impaired trafficking to increased protein expression. Many mutations caused only slight changes illustrating how sensitively the cerebellum reacts on impaired EAAT1 functions.

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Section: Introductionmentioning

confidence: 99%

Functional consequences of SLC1A3 mutations associated with episodic ataxia 6

et al. 2020

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“…Tremor and nystagmus are usually interictal signs. Responsiveness to AAA has been reported [116,117]). Piarroux et al [117] suggest to consider FGF14-related episodic ataxia as Episodic Ataxia type 9.…”

Section: Fgf14mentioning

confidence: 99%

“…It also regulates Ca v 2.1 channels [ 111 ] and is required for Purkinje cell spontaneous firing [ 112 ]. Several patients have been recently reported with an autosomal dominant episodic ataxia harboring FGF14 mutation [ 74 , 113 , 114 , 115 , 116 , 117 ]). Episodes have variable onset, frequency, and duration and are characterized by vertigo, dizziness, and unsteadiness often triggered by fever.…”

Section: Introductionmentioning

confidence: 99%

Episodic Ataxias: Faux or Real?

Giunti¹,

Mantuano

Frontali

2020

IJMS

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The term Episodic Ataxias (EA) was originally used for a few autosomal dominant diseases, characterized by attacks of cerebellar dysfunction of variable duration and frequency, often accompanied by other ictal and interictal signs. The original group subsequently grew to include other very rare EAs, frequently reported in single families, for some of which no responsible gene was found. The clinical spectrum of these diseases has been enormously amplified over time. In addition, episodes of ataxia have been described as phenotypic variants in the context of several different disorders. The whole group is somewhat confused, since a strong evidence linking the mutation to a given phenotype has not always been established. In this review we will collect and examine all instances of ataxia episodes reported so far, emphasizing those for which the pathophysiology and the clinical spectrum is best defined.

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“…EA is a clinically heterogeneous disorder characterized by recurrent spells of ataxia lasting minutes to hours [15] which has been associated over time to a number of genes besides CACNA1A and KCNA1 (CACNB4, SLC1A3, FGF14, SLC2A1, ATP1A3, PRRT2) accounting for the majority of cases [15,29]. To date, two patients with two different KCND3 mutations have been reported with EA as the main disease feature [15,20].…”

Section: Episodic Ataxia and Other Paroxysmal Motor And Non-motor Dismentioning

confidence: 99%

KCND3-Related Neurological Disorders: From Old to Emerging Clinical Phenotypes

Pollini

Galosi

Tolve

et al. 2020

IJMS

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KCND3 encodes the voltage-gated potassium ion channel subfamily D member 3, a six trans-membrane protein (Kv4.3), involved in the transient outward K+ current. KCND3 defect causes both cardiological and neurological syndromes. From a neurological perspective, Kv4.3 defect has been associated to SCA type 19/22, a complex neurological disorder encompassing a wide spectrum of clinical features beside ataxia. To better define the phenotypic spectrum and course of KCND3-related neurological disorder, we review the clinical presentation and evolution in 68 reported cases. We delineated two main clinical phenotypes according to the age of onset. Neurodevelopmental disorder with epilepsy and/or movement disorders with ataxia later in the disease course characterized the early onset forms, while a prominent ataxic syndrome with possible cognitive decline, movement disorders, and peripheral neuropathy were observed in the late onset forms. Furthermore, we described a 37-year-old patient with a de novo KCND3 variant [c.901T>C (p.Ser301Pro)], previously reported in dbSNP as rs79821338, and a clinical phenotype paradigmatic of the early onset forms with neurodevelopmental disorder, epilepsy, parkinsonism-dystonia, and ataxia in adulthood, further expanding the clinical spectrum of this condition.

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FGF14‐related episodic ataxia: delineating the phenotype of Episodic Ataxia type 9

Cited by 36 publications

References 18 publications

Functional consequences of SLC1A3 mutations associated with episodic ataxia 6

Functional consequences of SLC1A3 mutations associated with episodic ataxia 6

Episodic Ataxias: Faux or Real?

KCND3-Related Neurological Disorders: From Old to Emerging Clinical Phenotypes

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