Spinocerebellar ataxia 27 with a novel nonsense variant (Lys177X) in FGF14

Shiroh Miura, Kengo Kosaka, Ryuta Fujioka, Yusuke Uchiyama, Tomofumi Shimojo, Takuya Morikawa, Azusa Irie, Takayuki Taniwaki, Hiroki Shibata

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抄録

Spinocerebellar ataxia 27 (SCA27) is an autosomal dominant SCA caused by variants in the fibroblast growth factor 14 (FGF14) gene. We examined a Japanese SCA patient whose deceased father also suffered from SCA. The patient was a 63-year-old male. He graduated from junior high school but received no further education. The predominant complaint was slowly progressive dysarthria and gait disturbance, which appeared at age 47. He showed pathological saccadic dysmetria, saccadic intrusions into smooth pursuit eye movements, dysarthria, and limb and truncal ataxia. His gait was wide-based but he did not require a walking stick. Limb muscle strength was intact. Deep tendon reflexes were normal or slightly reduced. Pathological reflexes were absent. He demonstrated mildly impaired vibration sense in the lower limbs. There was no urinary dysfunction. Brain MRI showed cerebellar atrophy without brainstem involvement. We first confirmed the absence of repeat expansion in genes known to be responsible for SCAs 1–3, 6–8, 10, 12, 17, 36 and dentatorubral-pallidoluysian atrophy. By exome analysis, we identified a novel heterozygous variant (NM_004115, c.529A>T; Lys177X) in exon 4 of the FGF14 gene. This variant is expected to generate a truncated FGF14 protein lacking the heparin binding sites, those are likely to modify the activity of FGF14. We confirmed the absence of the variant in 502 healthy Japanese individuals by Sanger sequencing. There is no record of the variant in public databases. We conclude that the novel variation in FGF14 is causative for SCA27 in this patient.

元の言語英語
ページ(範囲)172-176
ページ数5
ジャーナルEuropean Journal of Medical Genetics
62
発行部数3
DOI
出版物ステータス出版済み - 3 1 2019

Fingerprint

Dysarthria
Ataxia
Gait
Progressive Myoclonic Epilepsy
Genes
Smooth Pursuit
Exome
Stretch Reflex
Abnormal Reflexes
Cerebellar Ataxia
Canes
Muscle Strength
Eye Movements
Vibration
Fathers
Brain Stem
Atrophy
Heparin
Lower Extremity
Exons

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

これを引用

Spinocerebellar ataxia 27 with a novel nonsense variant (Lys177X) in FGF14. / Miura, Shiroh; Kosaka, Kengo; Fujioka, Ryuta; Uchiyama, Yusuke; Shimojo, Tomofumi; Morikawa, Takuya; Irie, Azusa; Taniwaki, Takayuki; Shibata, Hiroki.

:: European Journal of Medical Genetics, 巻 62, 番号 3, 01.03.2019, p. 172-176.

研究成果: ジャーナルへの寄稿記事

Miura, S, Kosaka, K, Fujioka, R, Uchiyama, Y, Shimojo, T, Morikawa, T, Irie, A, Taniwaki, T & Shibata, H 2019, 'Spinocerebellar ataxia 27 with a novel nonsense variant (Lys177X) in FGF14', European Journal of Medical Genetics, 巻. 62, 番号 3, pp. 172-176. https://doi.org/10.1016/j.ejmg.2018.07.005
Miura S, Kosaka K, Fujioka R, Uchiyama Y, Shimojo T, Morikawa T その他. Spinocerebellar ataxia 27 with a novel nonsense variant (Lys177X) in FGF14. European Journal of Medical Genetics. 2019 3 1;62(3):172-176. https://doi.org/10.1016/j.ejmg.2018.07.005
Miura, Shiroh ; Kosaka, Kengo ; Fujioka, Ryuta ; Uchiyama, Yusuke ; Shimojo, Tomofumi ; Morikawa, Takuya ; Irie, Azusa ; Taniwaki, Takayuki ; Shibata, Hiroki. / Spinocerebellar ataxia 27 with a novel nonsense variant (Lys177X) in FGF14. :: European Journal of Medical Genetics. 2019 ; 巻 62, 番号 3. pp. 172-176.
@article{6bb6414a376049268b6f1ff95d77d3d2,
title = "Spinocerebellar ataxia 27 with a novel nonsense variant (Lys177X) in FGF14",
abstract = "Spinocerebellar ataxia 27 (SCA27) is an autosomal dominant SCA caused by variants in the fibroblast growth factor 14 (FGF14) gene. We examined a Japanese SCA patient whose deceased father also suffered from SCA. The patient was a 63-year-old male. He graduated from junior high school but received no further education. The predominant complaint was slowly progressive dysarthria and gait disturbance, which appeared at age 47. He showed pathological saccadic dysmetria, saccadic intrusions into smooth pursuit eye movements, dysarthria, and limb and truncal ataxia. His gait was wide-based but he did not require a walking stick. Limb muscle strength was intact. Deep tendon reflexes were normal or slightly reduced. Pathological reflexes were absent. He demonstrated mildly impaired vibration sense in the lower limbs. There was no urinary dysfunction. Brain MRI showed cerebellar atrophy without brainstem involvement. We first confirmed the absence of repeat expansion in genes known to be responsible for SCAs 1–3, 6–8, 10, 12, 17, 36 and dentatorubral-pallidoluysian atrophy. By exome analysis, we identified a novel heterozygous variant (NM_004115, c.529A>T; Lys177X) in exon 4 of the FGF14 gene. This variant is expected to generate a truncated FGF14 protein lacking the heparin binding sites, those are likely to modify the activity of FGF14. We confirmed the absence of the variant in 502 healthy Japanese individuals by Sanger sequencing. There is no record of the variant in public databases. We conclude that the novel variation in FGF14 is causative for SCA27 in this patient.",
author = "Shiroh Miura and Kengo Kosaka and Ryuta Fujioka and Yusuke Uchiyama and Tomofumi Shimojo and Takuya Morikawa and Azusa Irie and Takayuki Taniwaki and Hiroki Shibata",
year = "2019",
month = "3",
day = "1",
doi = "10.1016/j.ejmg.2018.07.005",
language = "English",
volume = "62",
pages = "172--176",
journal = "European Journal of Medical Genetics",
issn = "1769-7212",
publisher = "Elsevier Masson SAS",
number = "3",

}

TY - JOUR

T1 - Spinocerebellar ataxia 27 with a novel nonsense variant (Lys177X) in FGF14

AU - Miura, Shiroh

AU - Kosaka, Kengo

AU - Fujioka, Ryuta

AU - Uchiyama, Yusuke

AU - Shimojo, Tomofumi

AU - Morikawa, Takuya

AU - Irie, Azusa

AU - Taniwaki, Takayuki

AU - Shibata, Hiroki

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Spinocerebellar ataxia 27 (SCA27) is an autosomal dominant SCA caused by variants in the fibroblast growth factor 14 (FGF14) gene. We examined a Japanese SCA patient whose deceased father also suffered from SCA. The patient was a 63-year-old male. He graduated from junior high school but received no further education. The predominant complaint was slowly progressive dysarthria and gait disturbance, which appeared at age 47. He showed pathological saccadic dysmetria, saccadic intrusions into smooth pursuit eye movements, dysarthria, and limb and truncal ataxia. His gait was wide-based but he did not require a walking stick. Limb muscle strength was intact. Deep tendon reflexes were normal or slightly reduced. Pathological reflexes were absent. He demonstrated mildly impaired vibration sense in the lower limbs. There was no urinary dysfunction. Brain MRI showed cerebellar atrophy without brainstem involvement. We first confirmed the absence of repeat expansion in genes known to be responsible for SCAs 1–3, 6–8, 10, 12, 17, 36 and dentatorubral-pallidoluysian atrophy. By exome analysis, we identified a novel heterozygous variant (NM_004115, c.529A>T; Lys177X) in exon 4 of the FGF14 gene. This variant is expected to generate a truncated FGF14 protein lacking the heparin binding sites, those are likely to modify the activity of FGF14. We confirmed the absence of the variant in 502 healthy Japanese individuals by Sanger sequencing. There is no record of the variant in public databases. We conclude that the novel variation in FGF14 is causative for SCA27 in this patient.

AB - Spinocerebellar ataxia 27 (SCA27) is an autosomal dominant SCA caused by variants in the fibroblast growth factor 14 (FGF14) gene. We examined a Japanese SCA patient whose deceased father also suffered from SCA. The patient was a 63-year-old male. He graduated from junior high school but received no further education. The predominant complaint was slowly progressive dysarthria and gait disturbance, which appeared at age 47. He showed pathological saccadic dysmetria, saccadic intrusions into smooth pursuit eye movements, dysarthria, and limb and truncal ataxia. His gait was wide-based but he did not require a walking stick. Limb muscle strength was intact. Deep tendon reflexes were normal or slightly reduced. Pathological reflexes were absent. He demonstrated mildly impaired vibration sense in the lower limbs. There was no urinary dysfunction. Brain MRI showed cerebellar atrophy without brainstem involvement. We first confirmed the absence of repeat expansion in genes known to be responsible for SCAs 1–3, 6–8, 10, 12, 17, 36 and dentatorubral-pallidoluysian atrophy. By exome analysis, we identified a novel heterozygous variant (NM_004115, c.529A>T; Lys177X) in exon 4 of the FGF14 gene. This variant is expected to generate a truncated FGF14 protein lacking the heparin binding sites, those are likely to modify the activity of FGF14. We confirmed the absence of the variant in 502 healthy Japanese individuals by Sanger sequencing. There is no record of the variant in public databases. We conclude that the novel variation in FGF14 is causative for SCA27 in this patient.

UR - http://www.scopus.com/inward/record.url?scp=85049912469&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049912469&partnerID=8YFLogxK

U2 - 10.1016/j.ejmg.2018.07.005

DO - 10.1016/j.ejmg.2018.07.005

M3 - Article

C2 - 30017992

AN - SCOPUS:85049912469

VL - 62

SP - 172

EP - 176

JO - European Journal of Medical Genetics

JF - European Journal of Medical Genetics

SN - 1769-7212

IS - 3

ER -