Disease Information for Cerebellar ataxia/Cayman type

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Clinical Manifestations
Signs & Symptoms
Hypotonia
Action Tremor
Acute ataxia
Ataxia, Cerebellar type
Cerebellar signs
Dysarthria
Gait disturbance/abnormality
Mental Deficiency Child
Nystagmus
Nystagmus, convergence
Psychomotor regression/infant/child
Tremor,intention
Unsteadiness movement/Gait in a child
Psychomotor retardation
Difficulty Talking
True Vertigo Sign Confirmed
Disease Progression
Course/Prolonged/persistent/Not progressive
Demographics & Risk Factors
Travel, Geographic & Climate Related Factors
Residence/Travel/Grand Cayman Island
Family History
Family history/Ataxia
Family history/Nerve disease
Sex & Age Groups
Population/Child
Associated Diseases & Rule outs
Rule Outs
Ataxia-telangiectasia
Friedreich's Ataxia
Associated Disease & Complications
Cerebellar ataxia
Congenital Nystagmus
Mental retardation
Ataxia Disorder
Disease Mechanism & Classification
Pathophysiology
Pathophysiology/Gene ATCAY (Neuron protein caytaxin) mutation
Process
PROCESS/Autosomal recessive disorder (ex)
PROCESS/Hereditary developmental disorder (ex)
PROCESS/Hereditofamilial (category)
PROCESS/INCIDENCE/Extremely rare disease
PROCESS/Hereditary ataxia disorder (ex)
PROCESS/Hereditary SCA (spinocerebellar ataxias)
Definition

CEREBELLAR ATAXIA, CAYMAN TYPE; ATCAY; Gene map locus 19p13_3; Cayman cerebellar ataxia can be caused by mutation in the ATCAY gene (608179), which encodes the neuron-restricted protein caytaxin; Autosomal recessive Cayman cerebellar ataxia, identified by Johnson et al; (1978) in a population isolate on Grand Cayman Island, is characterized by marked psychomotor retardation and prominent nonprogressive cerebellar dysfunction including nystagmus, intention tremor, dysarthria, and wide-based ataxic gait; Hypotonia is present from early childhood. Retinal abnormalities are absent; Nystuen et al (1996) identified 19 affected individuals from this isolate; Based on the assumption of identity by descent (IBD) at the disease locus in affected individuals, they used a DNA pooling strategy to perform a genomewide screen of polymorphic markers to search for a genomic interval in linkage disequilibrium with the disease; Two affected pools (one contained DNA from all affected individuals, the other contained DNA from the 10 most closely related affected individuals) and a pool of DNA from unaffected sibs and parents of affected individuals were screened with 300 STRPs (short tandem repeat polymorphisms) (Sheffield et al, 1995); A single chromosome 19 marker, GATA66B01, was found to show a significantly different allele pattern consistent with IBD; Through analysis of additional proximal and distal markers on chromosome 19p13_3, Nystuen et al (1996) mapped the Cayman cerebellar ataxia gene to a 9-cM region between the flanking markers D19S424 and GATA66B01;

Comparative mapping suggested that the mouse mutation "jittery," which maps to the homologous region on mouse chromosome 10 (Kapfhamer et al, 1996), might be homologous to ATCAY; Because many spontaneous mouse mutations are caused by deletions or insertions, Bomar et al; (2003) screened all genes from the critical region of mouse chromosome 10 by Southern blot hybridization; One probe for an unknown predicted gene showed DNA changes in both jittery and the allelic "hesitant" mouse; In silico restriction mapping predicted the locations of the mutations as exon 4 and intron 1, respectively, and genomic PCRs showed larger products in each case; The insertion in exon 4 of jittery was the first mouse mutation caused by an Alu-related mutagenesis, which is common in humans (Kazazian and Moran, 1998); In individuals with Cayman ataxia, Bomar et al (2003) found homozygosity for 2 sequence variants in the ATCAY gene: a C-to-G change in exon 9, predicting a serine-to-arginine substitution at amino acid 301; and a G-to-T substitution in the third base of intron 9 (608179_0001); Both mutations completely segregated with the disorder and with carrier status in over 40 family members that were genotyped blindly; Neither mutation was found in any of more than 1,000 chromosomes from several different ethnic groups;

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