Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1386
pubmed:dateCreated
1999-8-26
pubmed:abstractText
Different aspects of expanded polyglutamine tracts and of their pathogenetic role are taken into consideration here. (i) The (CAG)n length of wild-type alleles of the Huntington disease gene was analysed in instability-prone tumour tissue from colon cancer patients to test whether the process leading to the elongation of alleles towards the expansion range involves single-unit stepwise mutations or larger jumps. The analysis showed that length changes of a single unit had a relatively low frequency. (ii) The observation of an expanded spinocerebellar ataxia (SCA)1 allele with an unusual pattern of multiple CAT interruptions showed that cryptic sequence variations are critical not only for sequence length stability but also for the expression of the disease phenotype. (iii) Small expansions of the (CAG)n sequence at the CACNA1A gene have been reported as causing SCA6. The analysis of families with SCA6 and episodic ataxia type 2 showed that these phenotypes are, in fact, expressions of the same disorder caused either by point mutations or by small (CAG)n expansions. A gain of function has been hypothesized for all proteins containing an expanded polyglutamine stretch, including the alpha 1A subunit of the voltage-gated calcium channel type P/Q coded by the CACNA1A gene. Because point mutations at the same gene with similar phenotypic consequences are highly unlikely to have this effect, an alternative common pathogenetic mechanism for all these mutations, including small expansions, can be hypothesized.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-1347772, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-7507480, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-7543989, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-7550343, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-7670474, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-7704024, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-7824128, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-7847859, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-7951324, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-7977376, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-8037204, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-8104707, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-8198139, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-8275090, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-8358429, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-8634720, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-8825276, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-8896557, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-8898206, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-8912795, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-8988170, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-9158152, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-9267033, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-9267034, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-9292723, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-9302278, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-9302293, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-9345107, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-9398841, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-9413985, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-9459004, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-9485421, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-9539441, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-9585597, http://linkedlifedata.com/resource/pubmed/commentcorrection/10434311-9600739
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0962-8436
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
354
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1089-94
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
CAG repeat instability, cryptic sequence variation and pathogeneticity: evidence from different loci.
pubmed:affiliation
Istituto di Medicina Sperimentale, CNR, Roma, Italy. marina.frontali@ims.rm.cnr.it
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't