Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently described an untranslated CTG expansion that causes a previously undescribed form of spinocerebellar ataxia (SCA8). The SCA8 CTG repeat is preceded by a polymorphic but stable CTA tract, with the configuration (CTA)(1-21)(CTG)(n). The CTG portion of the repeat is elongated on pathogenic alleles, which nearly always change in size when transmitted from generation to generation. To better understand the reduced penetrance and maternal penetrance bias associated with SCA8 we analyzed the sequence configurations and instability patterns of the CTG repeat in affected and unaffected family members. In contrast to other triplet repeat diseases, expanded alleles found in affected SCA8 individuals can have either a pure uninterrupted CTG repeat tract or an allele with one or more CCG, CTA, CTC, CCA or CTT interruptions. Surprisingly, we found six different sequence configurations of the CTG repeat on expanded alleles in a seven generation family. In two instances duplication of CCG interruptions occurred over a single generation and in other instances duplications that had occurred in different branches of the family could be inferred. We also evaluated SCA8 instability in sperm samples from individuals with expansions ranging in size from 80 to 800 repeats in blood. Surprisingly the SCA8 repeat tract in sperm underwent contractions, with nearly all of the resulting expanded alleles having repeat lengths of <100 CTGs, a size that is not often associated with disease. These en masse repeat contractions in sperm likely underlie the reduced penetrance associated with paternal transmission.
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PMID:SCA8 CTG repeat: en masse contractions in sperm and intergenerational sequence changes may play a role in reduced penetrance. 1095 51

Autosomal dominant leukodystrophy (ADLD) with autonomic symptoms is a slowly progressive leukodystrophy with an onset in the 4th to 6th decade of life. Early symptoms are derived from the autonomic nervous system with bladder dysfunction in the majority of patients. The disease progresses slowly with loss of fine motor skills, ataxia, and affected individuals may survive for two decades after onset of symptoms. The molecular basis behind ADLD remains unknown but the causative locus was previously mapped to a 4 cM region on chromosome 5. We have recently identified a large family of Swedish origin with this type of ADLD. Linkage analysis on samples from family members confirmed linkage to 5q23 and supports genetic homogeneity for the disease. We fine mapped and localized the ADLD gene to a 0.96 cM region between D5S1495 and CTT/CCT15. A maximum parametric multipoint location score of 9.45 was obtained for a position at the marker CTT55. From our results we conclude that the ADLD gene locus is restricted to a 1.47 Mbp interval containing 13 known or putative genes.
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PMID:Adult-onset autosomal dominant leukodystrophy with autonomic symptoms restricted to 1.5 Mbp on chromosome 5q23. 1682 6