Infant Spinocerebellar Ataxia Type 27: Early Presentation Due To a 13q33.1 Microdeletion Involving the FGF14 Gene

Tucker, Megan; Kalb, Fayth M.; Escobar, Luis

doi:10.4172/2157-7412.1000208

Cited by 5 publications

(15 citation statements)

References 17 publications

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“…However, since this initial description, an additional 19 patients, including our case, have been reported leading to expansion of the phenotype to include episodic ataxia and parkinsonism. [5][6][7][8][9][10][11][12][13][14][15][16][17] With the increased clinical information from the descriptions of 33 patients with SCA27 reported to date, we are better able to characterize the frequency of symptoms associated with this SCA and potentially improve our understanding of these symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…From these papers, a total of 38 individuals were identified by genetic testing, clinical examination, or family report of similar symptoms to gene-positive relatives. [5][6][7][8][9][10][11][12][13][14][15][16][17] Of the 38 patients reported, seven either did not have genetic confirmation of SCA27 or lacked any clinical examination information. One of these patients, however, was the father of two genetically confirmed, non-identical sons.…”

Section: Methodsmentioning

confidence: 99%

“…1,4 SCA27 was first reported in 2006, but the spectrum of phenotypic expression is only beginning to be elucidated. [5][6][7][8][9][10][11][12][13][14][15][16][17] We present here a patient who was found to have a novel, pathogenic mutation in the Fibroblast Growth Factor 14 (FGF14) gene located at chromosome 13q33, the gene associated with SCA27. We also provide a review of the literature in order to better characterize the phenotypic expression of this uncommon condition.…”

Section: Introductionmentioning

confidence: 99%

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Spinocerebellar Ataxia 27: A Review and Characterization of an Evolving Phenotype

Groth

Berman

2018

Tremor and Other Hyperkinetic Movements

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Background: Spinocerebellar ataxia (SCA) is an uncommon form of progressive cerebellar ataxia with multiple genetic causes and marked variability in phenotypic expression even across patients with identical genetic abnormalities. SCA27 is a recently identified SCA caused by mutations in the Fibroblast Growth Factor 14 gene, with a phenotypic expression that is only beginning to be fully appreciated. We report here a case of a 70-year-old male who presented with slowly worsening tremor and gait instability that began in his early adulthood along with additional features of parkinsonism on examination. Work-up revealed a novel pathogenic mutation in the Fibroblast Growth Factor 14 gene, and symptoms improved with amantadine and levodopa. We also provide a review of the literature in order to better characterize the phenotypic expression of this uncommon condition. Methods: Case report and review of the literature. Results: Review of the literature revealed a total of 32 previously reported clinical cases of SCA27. Including our case, we found that early-onset tremor (12.1 ¡ 10.5 years) was present in 95.8%, while gait ataxia tended to present later in life (23.7 ¡ 16.7 years) and was accompanied by limb ataxia, dysarthria, and nystagmus. Other features of SCA27 that may distinguish it from other SCAs include the potential for episodic ataxia, accompanying psychiatric symptoms, and cognitive impairment. Discussion: Testing for SCA27 should be considered in individuals with ataxia who report tremor as an initial or early symptom, as well as those with additional findings of episodic ataxia, neuropsychiatric symptoms, or parkinsonism.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Spinocerebellar Ataxia 27: A Review and Characterization of an Evolving Phenotype

Groth

Berman

2018

Tremor and Other Hyperkinetic Movements

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“…In humans, mutations in FGF14 are mostly associated with spinocerebellar ataxia type 27 (SCA27), part of a diverse group of autosomal dominant hereditary ataxias whereby affected individuals develop progressive incoordination [ 1 ]. The clinical features of humans with hereditary ataxias and FGF14 mutations are variable, most cases have been diagnosed in young children ranging in age from 8 months to 5 years [ 23 – 26 ]. However in one Dutch family, where 14 of 21 members of the family were affected, ataxia did not develop until 15–20 years of age, although trembling of the hands developed in childhood [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…Three of the reported mutations in FGF14 in humans with SCA27 involve heterozygous single-base mutations, two single-base pair deletions (c.487delA and c.10delC) [ 28 , 29 ] and a missense mutation (T145C) [ 27 ]. Other reported mutations in humans involve larger deletions, translocations and breakpoint events involving the FGF14 gene [ 23 – 26 ]. However, the scale of the mutation does not appear to affect the clinical presentation of the disease.…”

Section: Discussionmentioning

confidence: 99%

Familial episodic ataxia in lambs is potentially associated with a mutation in the fibroblast growth factor 14 (FGF14) gene

et al. 2017

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Familial episodic ataxia of lambs is a congenital transient autosomal dominant disorder of newborn lambs, with varying expressivity. Affected lambs show episodes of an asymmetric ataxic gait, base-wide extensor hypertonia of the thoracic limbs and flexor hypertonia of the pelvic limbs. The aim of the study was to determine the genetic variant causing familial episodic ataxia in lambs. Using whole genome sequencing of two half-sib affected lambs, their sire, and their two normal dams, a heterozygous C>T transition at OAR10:77593415 (Oar_v3.1) in exon 1 of the fibroblast growth factor 14 (FGF14) gene (c.46C>T) was identified. The c.46C>T transition resulted in a premature stop codon at position 16 of the 247 amino acid FGF14 protein (p.Q16*). PCR and Sanger sequencing was used to genotype an additional 20 clinically affected animals, demonstrating all lambs carried the c.46C>T variant but 1 clinically more severely affected inbred lamb was homozygous (TT). A further 11 unrelated normal ewes were positionally sequenced, none of which had the variant, while in 18 lambs of unknown status born over 2 years of breeding trials six lambs were found to have the c.46C>T variant, likely clinically unidentified heterozygotes due to the variable expressivity, while 12 did not. In conclusion, familial episodic ataxia of lambs is potentially associated with a c.46C>T variant in the FGF14 gene. Further research is required into the mechanism behind the apparent recovery of lambs.

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Fibroblast Growth Factor 14 Modulates the Neurogenesis of Granule Neurons in the Adult Dentate Gyrus

Alshammari

Nenov

et al. 2015

Mol Neurobiol

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Adult neurogenesis, the production of mature neurons from progenitor cells in the adult mammalian brain, is linked to the etiology of neurodegenerative and psychiatric disorders. However, a thorough understanding of the molecular elements at the base of adult neurogenesis remains elusive. Here, we provide evidence for a previously undescribed function of fibroblast growth factor 14 (FGF14), a brain disease-associated factor that controls neuronal excitability and synaptic plasticity, in regulating adult neurogenesis in the dentate gyrus (DG). We found that FGF14 is dynamically expressed in restricted subtypes of Sex Determining Region Y-Box 2 (Sox2) positive and doublecortin (DCX) positive neural progenitors in the DG. BrdU incorporation studies and confocal imaging revealed that genetic deletion of Fgf14 in Fgf14−/− mice leads to a significant change in the proportion of proliferating, and immature and mature newly born adult granule cells. This results in an increase in the late immature and early mature population of DCX and calretinin (CR) positive neurons. Electrophysiological extracellular field recordings showed reduced minimal threshold response and impaired paired-pulse facilitation at the perforant path to DG inputs in Fgf14−/− compared to Fgf14+/+ mice, supporting disrupted synaptic connectivity as a correlative read-out to impaired neurogenesis. These new insights into the biology of FGF14 in neurogenesis shed light into the signaling pathways associated with disrupted functions in complex brain diseases.

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Infant Spinocerebellar Ataxia Type 27: Early Presentation Due To a 13q33.1 Microdeletion Involving the FGF14 Gene

Cited by 5 publications

References 17 publications

Spinocerebellar Ataxia 27: A Review and Characterization of an Evolving Phenotype

Spinocerebellar Ataxia 27: A Review and Characterization of an Evolving Phenotype

Familial episodic ataxia in lambs is potentially associated with a mutation in the fibroblast growth factor 14 (FGF14) gene

Fibroblast Growth Factor 14 Modulates the Neurogenesis of Granule Neurons in the Adult Dentate Gyrus

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