Document Detail


Instability of a premutation allele in homozygous patients with myotonic dystrophy type 1.
MedLine Citation:
PMID:  12325072     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Myotonic dystrophy type 1 (DM1) is caused by the expansion of an unstable CTG repeat in the DMPK gene on chromosome 19q13.3. We present two siblings with DM1 who each inherited a premutation allele, (CTG)43, stably transmitted from the mother and a full-mutation allele, either (CTG)500 or (CTG)180, derived from a paternal protomutation allele, (CTG)52. Small-pool polymerase chain reaction analysis showed that the (CTG)52 repeat allele was relatively stable in somatic tissues but was highly unstable in the male germline and extremely biased toward further expansion, consistent with the high levels of anticipation observed in DM1 families. The (CTG)43 allele showed subtle somatic instability in the mother, with maximum additions of two repeats and deletions of one repeat. Conversely, in the younger affected siblings the (CTG)43 allele showed a high degree of somatic instability (approximately 70% mutation load), resulting in deletions reverting to the high end of the normal range (down to [CTG]33) and additions up to the proto-mutation range (up to [CTG]64). The difference in the somatic stability of the (CTG)43 allele between the mother and her offspring suggests that interallelic interactions or other mechanisms in trans regulate the stability of the (CTG)43 premutation allele.
Authors:
Claudia Abbruzzese; Sandro Costanzi Porrini; Bruno Mariani; Fiona K Gould; John P McAbney; Darren G Monckton; Tetsuo Ashizawa; Manlio Giacanelli
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of neurology     Volume:  52     ISSN:  0364-5134     ISO Abbreviation:  Ann. Neurol.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-09-26     Completed Date:  2002-10-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7707449     Medline TA:  Ann Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  435-41     Citation Subset:  IM    
Affiliation:
Dipartimento Medico-Chirurgico di Neuroscienze, Laboratorio di Istopatologia e Neurogenetica Molecolare, Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Alleles
Family Health
Female
Homozygote
Humans
Male
Myotonic Dystrophy / genetics*
Pedigree
Phenotype
Trinucleotide Repeat Expansion / genetics

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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