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X‐linked nonprogressive congenital cerebellar hypoplasia: Clinical description and mapping to chromosome Xq
Author(s) -
Illarioshkin Sergei N.,
Tanaka Hajime,
Tsuji Shoji,
Markova Elena D.,
Nikolskay Natalya N.,
IvanovaSamolenskay Irina A.
Publication year - 1996
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410400113
Subject(s) - cerebellar hypoplasia (non human) , cerebellar ataxia , hypoplasia , ataxia , dysarthria , genetics , locus (genetics) , x chromosome , genetic linkage , medicine , biology , cerebellum , neuroscience , anatomy , audiology , gene
We examined a large family in which an X‐linked recessive congenital ataxia manifested in 7 males from three generations. The affected boys first exhibited a marked delay of early developmental motor milestones. A neurological syndrome became evident by 5 to 7 years of age and included cerebellar ataxia, dysarthria, and external ophthalmoplegia; there were no symptoms of mental retardation, spastic paraparesis, or sensory loss. Neuroimaging studies revealed hypoplasia of cerebellar hemispheres and vermis. The disease showed no progression beyond early childhood. The unique heredity and clinical features clearly distinguish this new entity from a variety of previously described familial ataxias. Pairwise linkage analysis and haplotype reconstruction allowed us to map the gene responsible for this disorder to a 38‐cM interval on chromosome Xp11.21‐q24 flanked by the loci DXS991 and DXS1001. Upon multipoint linkage analysis, the disease gene was determined to be located most likely in the proximal part of chromosome Xq, with the maximal lod score of 4.66 at the locus DXS1059 (Xq23). This is the first example of the genetic mapping of a pure congenital cerebellar hypoplasia syndrome.