Genetic anticipation in Portuguese kindreds with familial amyloidotic polyneuropathy is unlikely to be caused by triplet repeat expansions

• Type: Article in International Scientific Journal
• Date: 1999

Authors

Soares, M (Author) Other; Buxbaum, J (Author) Other; Sirugo, G (Author) Other; Coelho, T (Author) Other; Alda Sousa (Author) ICBAS; Kastner, D (Author) Other; Maria Joao Saraiva (Author) ICBAS

Journal

Title: Human Genetics

Vol. 104

Pages: 480-485

ISSN: 0340-6717

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 27 Citations

Scopus - 31 Citations

Other information

Authenticus ID: P-001-468

DOI: 10.1007/s004390050991

Abstract (EN): Familial amyloidotic polyneuropathy (FAP) is a lethal autosomal dominant type of amyloidosis resulting from the deposition of transthyretin (ATTR) variants in the peripheral and autonomic nervous systems. ATTR V30M-associated FAP exhibits marked genetic anticipation in some families, with clinical symptoms developing at an earlier age in successive generations. The genetic basis of this phenomenon in FAP is unknown. Anticipation has been associated with the dynamic expansion of trinucleotide repents in several neurodegenerative disorders, such as Huntington disease, myotonic dystrophy, and fragile X syndrome. We have used the repeat expansion detection (RED) assay to screen affected members of Portuguese FAP kindreds for expansion of any of the ten possible trinucleotide repeats. Nine generational pairs with differences in their age of onset greater than 12 years and a control pair with identical ages of onset were tested. No major differences were found in the lengths of the ten trinucleotide repeats analyzed, The distribution of the maximal repeat sizes was consistent with reported studies in unrelated individuals with no known genetic disease, The present data do not support a role for trinucleotide repeat expansions as the molecular mechanism underlying anticipation in Portuguese FAP.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6