Familial spinocerebellar ataxia with cerebellar atrophy, peripheral neuropathy, and elevated level of serum creatine kinase, γ‐globulin, and α‐fetoprotein

Watanabe, Mitsunori; Sugai, Yoshiro; Concannon, Patrick; Kœnig, M.; Schmitt, Michèle; Sato, Madoka; Shizuka, Masami; Mizushima, Koichi; Ikeda, Yoshio; Tomidokoro, Yasushi; Okamoto, Koichi; Shoji, Mikio

doi:10.1002/ana.410440220

Cited by 55 publications

(34 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…12 Briefly, onset was around 20 years in all four cases; the patients, born of first-degree consanguineous parents, had spinocerebellar ataxia with cerebellar atrophy, telangiectasia over the bulbar conjunctiva and elevated α-foetoprotein. However, γ-globulins were also elevated and the diagnosis of a mild form of ataxiatelangiectasia was excluded by linkage studies.…”

Section: Subjectsmentioning

confidence: 93%

See 1 more Smart Citation

Homozygosity mapping of spinocerebellar ataxia with cerebellar atrophy and peripheral neuropathy to 9q33–34, and with hearing impairment and optic atrophy to 6p21–23

et al. 2000

Self Cite

View full text Add to dashboard Cite

With the availability of a simple molecular test that distinguishes Friedreich ataxia, the most frequent form of inherited ataxia, from other recessive ataxias, it now becomes possible to unravel the genetic heterogeneity of the latter. We have now localised two genes causing autosomal recessive spinocerebellar ataxia in two consanguineous families. In the first family, the four affected Japanese sibs had spinocerebellar ataxia associated with elevated levels of serum creatine kinase, γ-globulin, and α-foetoprotein. Homozygosity over a 20 cM region allowed to demonstrate linkage at 9q33.3-34.3 with a lod score of 3.0. Genotyping two unrelated Japanese patients from first degree consanguineous parents revealed that one was homozygous for the same region but did not share the biochemical features. In the second family, an Israeli uncle and a niece were affected by an early-onset recessive ataxia and subsequently developed hearing impairment and optic atrophy. Homozygosity over a 17 cM region allowed demonstration of linkage at 6p21-23 with a lod score of 3.25. These two localisations of autosomal recessive ataxia genes represent a first step toward the identification of genetically homogenous, non-Friedreich, ataxic patients and subsequent cloning of the genes. European Journal of Human Genetics (2000) 8, 986-990.

show abstract

Section: Subjectsmentioning

confidence: 93%

“…Creatine kinase was moderately elevated, vitamin E level was normal, as well as all other biological tests. 12 The father is deceased and samples of the healthy sibs were not available for study.…”

Section: Subjectsmentioning

confidence: 99%

Homozygosity mapping of spinocerebellar ataxia with cerebellar atrophy and peripheral neuropathy to 9q33–34, and with hearing impairment and optic atrophy to 6p21–23

et al. 2000

Self Cite

View full text Add to dashboard Cite

show abstract

“…A new type was recently reported, 39 but the disease was different in terms of conjunctival telangiectasias as a pathognomonic feature and elevated serum creatine kinase, gamma globulin, and ␣-fetoprotein levels as abnormal laboratory findings. Two reports on testing large groups of patients with recessive or sporadic ataxia for the main mutation in the FRDA gene have recently been published.…”

Section: Figure 2 (A) Mri Of Patient Iii-7 At Age 32 Coronal T2-weimentioning

confidence: 99%

Adult-onset autosomal recessive ataxia with thalamic lesions in a Finnish family

Rantamäki

Krahe²,

Paetau

et al. 2001

Neurology

View full text Add to dashboard Cite

Article abstract-Objective: To describe an unusual kindred with adult-onset ataxia and thalamic lesions detected by brain MRI. Methods: The authors characterized clinical, laboratory, and pathologic features of the disease and sought linkage to previously recognized ataxia loci. Results: Two sisters and a brother developed progressive ataxia, dysarthria, mild cognitive impairment, and sensorimotor neuropathy at age 30, combined with epilepsy in one sibling. MRI showed symmetric thalamic lesions, changes in brainstem gray matter, and white matter changes in the cerebellum. Autopsy in one of the patients revealed neuronal degeneration with a peculiar vacuolar change in thalamus, probably representing transsynaptic degeneration in response to deafferentation. Neuronal and secondary tract degeneration was observed in the spinal cord, cerebellum, and brainstem suggesting a spinocerebellar degeneration. The disorder appears to be transmitted as an autosomal recessive trait. Genetic and sequence analysis of the FRDA gene and comprehensive laboratory examinations excluded Friedreich's ataxia and other similar recessive diseases. Conclusion: Adult-onset recessive ataxia with bilateral thalamic lesions in this family may represent a distinct hereditary spinocerebellar ataxia.

show abstract

“…AOA2 was described initially in a Japanese family, 13 and to our knowledge, the present family is the fifth with genetically proven AOA2 in Japan 2,8,13-15 (H Takashima, personal communication). Mutations in SETX identified in Japanese AOA2 families are heterogeneous, except M271I, which has been found in two unrelated Japanese families 2,8,15 (H Takashima, personal communication).…”

Section: Discussionmentioning

confidence: 72%

A novel nonsense mutation in a Japanese family with ataxia with oculomotor apraxia type 2 (AOA2)

et al. 2009

View full text Add to dashboard Cite

We report a 67-year-old Japanese woman with ataxia with oculomotor apraxia type 2 (AOA2). She was born to consanguineous parents and showed a teenage onset, a slowly progressive cerebellar ataxia and sensory-motor neuropathy and an elevated level of serum a-fetoprotein (AFP). All of these clinical features were consistent with typical AOA2. She lacked oculomotor apraxia, as frequently observed in previously reported AOA2 patients. She was homozygous for a novel nonsense mutation, Glu385Ter (E385X), in the senataxin gene (SETX). To our knowledge, this is the fifth Japanese family with genetically confirmed AOA2. The mutations in SETX in Japanese AOA2 families are heterogeneous, except for M274I, which has been found in two unrelated families. More extensive screening by serum AFP followed by molecular genetic analysis of SETX in patients with Friedreich's ataxia-like phenotype may show that AOA2 is more common in Japan than previously thought. Keywords: ataxia with oculomotor apraxia type 2 (AOA2); sensory-motor neuropathy; senataxin; fiber type grouping Ataxia with oculomotor apraxia type 2 (AOA2) is a rare form of autosomal-recessive cerebellar ataxias associated with axonal sensorymotor neuropathy. 1 The disease-causing gene (SETX) encodes a protein, senataxin, with a homology to the fungal Sen1p protein. 2 SETX, which is composed of 2677 amino acids, contains a DNA/RNA helicase domain (1931-2446 amino acids) near the C terminus, and is likely to have important roles in DNA repair and transcription, and RNA processing. [2][3][4] The N-terminal domain (64-593 amino acids) of SETX is considered a putative protein interaction domain essential for proper localization of SETX. 5 To date, more than 50 mutations have been identified in AOA2 families worldwide. 1,2,[6][7][8][9][10][11][12] The mutations are distributed across the entire gene, without any specific mutation hot spots. Most of the mutations are frameshift, or nonsense mutations, supporting that a loss of function of SETX is critical for the development of AOA2.In this study, we describe a 67-year-old Japanese patient with AOA2 who carried a novel homozygous nonsense mutation, Glu385Ter (E385X), in SETX. Consistent with a prolonged clinical course, she showed prominent fiber type grouping in muscle biopsy. This study identifies the fifth Japanese family with genetically confirmed AOA2 2,8,13-15 (H Takashima, personal communication). CASE REPORTThe patient was a 67-year-old Japanese woman, who was born to consanguineous parents and attained normal developmental milestones during infancy. At B17 years old, she began falling frequently while walking. At age 20, she was referred to the hospital because of an unsteady gait. Soon thereafter, she was diagnosed with cerebellar ataxia, and by age 22, she could not walk without assistance. At B40 years old, she began to show speech disturbance and became clumsy with her hands.She had her first extensive medical examinations at age 46. Neurological examination showed horizontal gaze nystagmus and dysarthria, but ...

show abstract

Familial spinocerebellar ataxia with cerebellar atrophy, peripheral neuropathy, and elevated level of serum creatine kinase, γ‐globulin, and α‐fetoprotein

Cited by 55 publications

References 18 publications

Homozygosity mapping of spinocerebellar ataxia with cerebellar atrophy and peripheral neuropathy to 9q33–34, and with hearing impairment and optic atrophy to 6p21–23

Homozygosity mapping of spinocerebellar ataxia with cerebellar atrophy and peripheral neuropathy to 9q33–34, and with hearing impairment and optic atrophy to 6p21–23

Adult-onset autosomal recessive ataxia with thalamic lesions in a Finnish family

A novel nonsense mutation in a Japanese family with ataxia with oculomotor apraxia type 2 (AOA2)

Contact Info

Product

Resources

About