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Comprehensive phenotype of the p.Arg420his allelic form of spinocerebellar ataxia type 13.

Subramony SH, Advincula J, Perlman S, Rosales RL, Lee LV, Ashizawa T, Waters MF - Cerebellum (2013)

Bottom Line: The p.Arg420His allelic form of spinocerebellar ataxia type 13 has been reported in a large Filipino kindred, as well as three European index cases, one with an affected offspring.Haplotype analysis has confirmed independent mutational events.However, a comprehensive phenotypic description has yet to be published on SCA13(p.Arg420His).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Florida College of Medicine, Box 100296, Gainesville, FL, 32610, USA.

ABSTRACT
The p.Arg420His allelic form of spinocerebellar ataxia type 13 has been reported in a large Filipino kindred, as well as three European index cases, one with an affected offspring. Haplotype analysis has confirmed independent mutational events. All individuals share adult-onset, predominantly cerebellar signs and a slowly progressive course. However, a comprehensive phenotypic description has yet to be published on SCA13(p.Arg420His). In this study, we present the results of a detailed neurological clinical and diagnostic testing on 21 mutation-positive members of a four-generation Filipino family to further define this disease, aiding diagnosis and prognosis.

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Related in: MedlinePlus

Pedigree showing an extended SCA13 Filipino family. Filled black symbols are clinically affected individuals with known c.1259G>A genotype. Gray symbols represent asymptomatic examined individuals with known genotype. White insets indicate two wild-type alleles. Of the remaining 12 at-risk individuals, nine are c.1259G>A heterozygotes and three are wild type. They are not identified for privacy concerns. Bold numbers indicate the ages at examination and disease onset
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Fig1: Pedigree showing an extended SCA13 Filipino family. Filled black symbols are clinically affected individuals with known c.1259G>A genotype. Gray symbols represent asymptomatic examined individuals with known genotype. White insets indicate two wild-type alleles. Of the remaining 12 at-risk individuals, nine are c.1259G>A heterozygotes and three are wild type. They are not identified for privacy concerns. Bold numbers indicate the ages at examination and disease onset

Mentions: Forty-one members of a four-generation Filipino kindred segregating the KCNC3p.Arg420His allele were comprehensively examined, and blood samples were collected for mutation detection (Fig. 1). Data obtained included detailed medical and neurological histories: full neurological examination to obtain information on their oculomotor, bulbar, cerebellar, upper motor neuron, lower motor neuron, extrapyramidal and peripheral nervous systems, Montreal Cognitive Assessment (MoCA-P, Philippine version 7.1, 2010 administered by a trained local neuropsychologist), Scale for Assessment and Rating of Ataxia (SARA) score [7], “functional stage” indicating mobility status [8] (grade 0 being asymptomatic and grade 6 being bedbound and needing full help with activities of daily living), activities of daily living scale (Unified Huntington’s Disease Rating Scale (UHDRS IV)), and EQ-5D self-assessed quality of life scale. All data were obtained prior to mutation testing. Three affected members had nerve conduction studies performed. One underwent a 1-h sleep/awake EEG. MR imaging of the brain was obtained in five individuals, II-1, II-14, III-1, IV-1, and III-3. Serial scans for a mother–daughter pair (II-1/III-2) with a 5-year interval are included for longitudinal comparison. University of Florida Institutional Review Board approval for this study and signed informed consents for all patients have been retained. The original report of this family was limited to 11 affected individuals (I-1, II-1, II-4, II-5, II-6, II-7, II-10, II-14, III-2, III-3, and III-4) examined only for cerebellar, gait, and motor system abnormalities [2].Fig. 1


Comprehensive phenotype of the p.Arg420his allelic form of spinocerebellar ataxia type 13.

Subramony SH, Advincula J, Perlman S, Rosales RL, Lee LV, Ashizawa T, Waters MF - Cerebellum (2013)

Pedigree showing an extended SCA13 Filipino family. Filled black symbols are clinically affected individuals with known c.1259G>A genotype. Gray symbols represent asymptomatic examined individuals with known genotype. White insets indicate two wild-type alleles. Of the remaining 12 at-risk individuals, nine are c.1259G>A heterozygotes and three are wild type. They are not identified for privacy concerns. Bold numbers indicate the ages at examination and disease onset
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824261&req=5

Fig1: Pedigree showing an extended SCA13 Filipino family. Filled black symbols are clinically affected individuals with known c.1259G>A genotype. Gray symbols represent asymptomatic examined individuals with known genotype. White insets indicate two wild-type alleles. Of the remaining 12 at-risk individuals, nine are c.1259G>A heterozygotes and three are wild type. They are not identified for privacy concerns. Bold numbers indicate the ages at examination and disease onset
Mentions: Forty-one members of a four-generation Filipino kindred segregating the KCNC3p.Arg420His allele were comprehensively examined, and blood samples were collected for mutation detection (Fig. 1). Data obtained included detailed medical and neurological histories: full neurological examination to obtain information on their oculomotor, bulbar, cerebellar, upper motor neuron, lower motor neuron, extrapyramidal and peripheral nervous systems, Montreal Cognitive Assessment (MoCA-P, Philippine version 7.1, 2010 administered by a trained local neuropsychologist), Scale for Assessment and Rating of Ataxia (SARA) score [7], “functional stage” indicating mobility status [8] (grade 0 being asymptomatic and grade 6 being bedbound and needing full help with activities of daily living), activities of daily living scale (Unified Huntington’s Disease Rating Scale (UHDRS IV)), and EQ-5D self-assessed quality of life scale. All data were obtained prior to mutation testing. Three affected members had nerve conduction studies performed. One underwent a 1-h sleep/awake EEG. MR imaging of the brain was obtained in five individuals, II-1, II-14, III-1, IV-1, and III-3. Serial scans for a mother–daughter pair (II-1/III-2) with a 5-year interval are included for longitudinal comparison. University of Florida Institutional Review Board approval for this study and signed informed consents for all patients have been retained. The original report of this family was limited to 11 affected individuals (I-1, II-1, II-4, II-5, II-6, II-7, II-10, II-14, III-2, III-3, and III-4) examined only for cerebellar, gait, and motor system abnormalities [2].Fig. 1

Bottom Line: The p.Arg420His allelic form of spinocerebellar ataxia type 13 has been reported in a large Filipino kindred, as well as three European index cases, one with an affected offspring.Haplotype analysis has confirmed independent mutational events.However, a comprehensive phenotypic description has yet to be published on SCA13(p.Arg420His).

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Florida College of Medicine, Box 100296, Gainesville, FL, 32610, USA.

ABSTRACT
The p.Arg420His allelic form of spinocerebellar ataxia type 13 has been reported in a large Filipino kindred, as well as three European index cases, one with an affected offspring. Haplotype analysis has confirmed independent mutational events. All individuals share adult-onset, predominantly cerebellar signs and a slowly progressive course. However, a comprehensive phenotypic description has yet to be published on SCA13(p.Arg420His). In this study, we present the results of a detailed neurological clinical and diagnostic testing on 21 mutation-positive members of a four-generation Filipino family to further define this disease, aiding diagnosis and prognosis.

Show MeSH
Related in: MedlinePlus