title: Phenotypical spectrum of cerebellar ataxia associated with a novel mutation in the CA8 gene, encoding carbonic anhydrase (CA) VIII.
abstract: We define the neurological characteristics of familial cases from multiple branches of a large consanguineous family with cerebellar ataxia, mental retardation (MR), and dysequilibrium syndrome type 3 caused by a mutation in the recently cloned CA8 gene. The linkage analysis revealed a high logarithm of the odds (LOD) score region on 8q that harbors the CA8 in which a novel homozygous c.484G>A (p.G162R) mutation was identified in all seven affected members. The patients had variable cerebellar ataxia and mild cognitive impairment without quadrupedal gait. The brain MRI showed variable cerebellar volume loss and ill-defined peritrigonal white matter abnormalities. The Fluorodeoxyglucose Positron Emission Tomography (FDG PET) revealed hypometabolic cerebellar hemispheres, temporal lobes, and mesial cortex. This report expands the neurological and radiological phenotype associated with CA8 mutations. CA8 involvement should be considered in the differential diagnosis of other genetically unresolved autosomal recessive cerebellar ataxias.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Namik
authors.initials: N
authors.lastname: Kaya
authors.forename: Hesham
authors.initials: H
authors.lastname: Aldhalaan
authors.forename: Banan
authors.initials: B
authors.lastname: Al-Younes
authors.forename: Dilek
authors.initials: D
authors.lastname: Colak
authors.forename: Taghreed
authors.initials: T
authors.lastname: Shuaib
authors.forename: Fahad
authors.initials: F
authors.lastname: Al-Mohaileb
authors.forename: Abdulaziz
authors.initials: A
authors.lastname: Al-Sugair
authors.forename: Michael
authors.initials: M
authors.lastname: Nester
authors.forename: Suad
authors.initials: S
authors.lastname: Al-Yamani
authors.forename: Albandary
authors.initials: A
authors.lastname: Al-Bakheet
authors.forename: Nadia
authors.initials: N
authors.lastname: Al-Hashmi
authors.forename: Moeen
authors.initials: M
authors.lastname: Al-Sayed
authors.forename: Brian
authors.initials: B
authors.lastname: Meyer
authors.forename: Heinz
authors.initials: H
authors.lastname: Jungbluth
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Owain
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002524:Cerebellar Ataxia / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D053263:Gene Regulatory Networks / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D049268:Positron-Emission Tomography; D055815:Young Adult; D002256:Carbonic Anhydrases; D047908:Intracellular Signaling Peptides and Proteins
chemical_list: D014408:Biomarkers, Tumor; C512818:CA8 protein, human; D002256:Carbonic Anhydrases; D047908:Intracellular Signaling Peptides and Proteins