title: Autosomal dominant congenital non-progressive ataxia overlaps with the SCA15 locus.
abstract: BACKGROUND
  Most patients with pure nonprogressive congenital cerebellar ataxia have a sporadic form of unknown heredity and etiology. Several small families have been reported with a dominantly inherited nonprogressive congenital ataxia (NPCA).
  
  
  METHODS
  The authors ascertained and clinically characterized a four-generation pedigree segregating an autosomal dominant type of congenital nonprogressive cerebellar ataxia associated with cognitive impairment. Following the exclusion of several SCA localizations (SCA-1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 17, IOSCA, and DRPLA), a genome-wide linkage study was performed.
  
  
  RESULTS
  Examination of the family showed that all affected members had gait ataxia and cognitive disability with variable features of dysarthria, dysmetria, dysdiadochokinesia, nystagmus, dystonic movements, and cerebellar hypoplasia on imaging. Clinical signs of pyramidal tract dysfunction and sensory changes were absent. A genome-wide search in this family detected linkage to chromosome 3p with a maximum two-point lod score of 4.26 at D3S3630. This localization to the pter is distal to D3S1304, as defined by a recombination event. This overlaps with the SCA15 locus, with the critical overlapping region between the microsatellite markers, D3S1304 and D3S1620 (approximately 8 cM).
  
  
  CONCLUSIONS
  Autosomal dominant congenital nonprogressive cerebellar ataxia with or without cerebellar hypoplasia overlaps with the SCA15 locus on chromosome 3pter.
authors.affiliation: Hunter Genetics, PO Box 84, Waratah, Newcastle, NSW, Australia. tracy.dudding@hunter.health.nsw.gov.au
authors.forename: T E
authors.initials: TE
authors.lastname: Dudding
authors.forename: K
authors.initials: K
authors.lastname: Friend
authors.forename: P W
authors.initials: PW
authors.lastname: Schofield
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: I A
authors.initials: IA
authors.lastname: Wilkinson
authors.forename: R I
authors.initials: RI
authors.lastname: Richards
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics; D004401:Dysarthria / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D005819:Genetic Markers; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007805:Language Development Disorders / Q000235:genetics; D008126:Lod Score; D008279:Magnetic Resonance Imaging; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011596:Psychomotor Disorders / Q000235:genetics; D013132:Spinocerebellar Degenerations / Q000151:congenital / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins