Overcoming artefact: anticipation in 284 Portuguese kindreds with familial amyloid polyneuropathy (FAP) ATTRV30M

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Lemos, C (Author) ICBAS; Coelho, T (Author) Other; Alves Ferreira, M (Author) Other; Martins da Silva, A (Author) Other; Sequeiros, J (Author) ICBAS; Mendonca, D (Author) ICBAS; Sousa, A (Author) ICBAS

Journal

Title: Journal of Neurology, Neurosurgery and Psychiatry

Vol. 85

Pages: 326-330

ISSN: 0022-3050

Publisher: BMJ PUBLISHING GROUP

Indexing

ISI Web of Knowledge - 51 Citations

Scopus - 52 Citations

Other information

Authenticus ID: P-008-EE0

DOI: 10.1136/jnnp-2013-305383

Abstract (EN): Background Early-onset (40years) and later-onset (50years) cases of familial amyloid polyneuropathy (FAP) ATTRV30M are not different entities, often coexisting in the same family, and showing anticipation (earlier age-at-onset (AO) in younger generations, usually associated with more severe phenotype). Historically, anticipation has been ascribed to ascertainment biases. Our aim was to study anticipation in a very large number of FAP kindreds, removing possible biases, and gain further insight into parent-of-origin effects. Methods We analysed 926 parent-offspring pairs (from the Unidade Clinica de Paramiloidose roster, collected in 70years), both clinically observed and had well-established AO, correcting for intrafamilial correlations. Results Women had a significantly higher AO, either for daughters (mean: 33.70, SD: 6.84) vs sons (29.43, 6.08); or mothers (39.57, 11.75) vs fathers (35.62, 11.62). Also, 291 pairs showed marked anticipation (10years); the transmitting parent was the mother in 203 pairs. Mother-son pairs showed larger anticipation (10.43, 9.34), while father-daughter pairs showed only a residual anticipation (1.23, 9.77). Gender of offspring and parents was highly significant (with no interaction). To remove possible biases, we repeated analyses: (1) excluding the proband; (2) removing pairs with simultaneous onset; and (3) excluding offspring born after 1960. Anticipation was found in all subsamples, with the same trend for a parent-of-origin effect. Noteworthy, parents with AO 40 years never had offspring with AO 50. Conclusions These findings confirm anticipation as a true biological phenomenon, also in FAP ATTRV30M. Acknowledgment of anticipation may have important clinical implications in genetic counselling of offspring and in follow-up of mutation carriers.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5