Insights into the genetic epidemiology of spinal and bulbar muscular atrophy: prevalence estimation and multiple founder haplotypes in the Veneto Italian region.


Journal

European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311

Informations de publication

Date de publication:
03 2019
Historique:
received: 08 08 2018
accepted: 18 10 2018
pubmed: 24 10 2018
medline: 20 8 2019
entrez: 24 10 2018
Statut: ppublish

Résumé

Literature data on spinal and bulbar muscular atrophy (SBMA) epidemiology are limited and restricted to specific populations. The aim of our study was to accurately collect information about SBMA patients living in the Veneto region in Italy to compute reliable epidemiological data. Androgen receptor (AR) lineages were genotyped to evaluate the presence of a founder effect. A prevalence survey considering all SBMA patients diagnosed in the Italian Veneto region on 31 January 2018 was carried out. The presence of different haplotypes obtained genotyping 15 polymorphic markers (single nucleotide polymorphisms and short tandem repeats) around the AR gene was evaluated. Based on 68 patients, the punctual prevalence of the disease on 31 January 2018 was 2.58/100 000 (95% confidence interval 1.65-3.35) in the male population. Five different haplotypes were identified, confirming the existence of multiple founder effects. It was also observed that, within the same haplotype, patients had a similar CAG repeat number (P-value < 0.001). A reliable estimation of SBMA prevalence in the Italian Veneto region was calculated which does not seem to be affected by a strong founder effect. Moreover, our data suggest that the length of the CAG expansion could be preserved in patients harbouring the same haplotype.

Sections du résumé

BACKGROUND AND PURPOSE
Literature data on spinal and bulbar muscular atrophy (SBMA) epidemiology are limited and restricted to specific populations. The aim of our study was to accurately collect information about SBMA patients living in the Veneto region in Italy to compute reliable epidemiological data. Androgen receptor (AR) lineages were genotyped to evaluate the presence of a founder effect.
METHODS
A prevalence survey considering all SBMA patients diagnosed in the Italian Veneto region on 31 January 2018 was carried out. The presence of different haplotypes obtained genotyping 15 polymorphic markers (single nucleotide polymorphisms and short tandem repeats) around the AR gene was evaluated.
RESULTS
Based on 68 patients, the punctual prevalence of the disease on 31 January 2018 was 2.58/100 000 (95% confidence interval 1.65-3.35) in the male population. Five different haplotypes were identified, confirming the existence of multiple founder effects. It was also observed that, within the same haplotype, patients had a similar CAG repeat number (P-value < 0.001).
CONCLUSIONS
A reliable estimation of SBMA prevalence in the Italian Veneto region was calculated which does not seem to be affected by a strong founder effect. Moreover, our data suggest that the length of the CAG expansion could be preserved in patients harbouring the same haplotype.

Identifiants

pubmed: 30351503
doi: 10.1111/ene.13850
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Pagination

519-524

Subventions

Organisme : Telethon
Pays : Italy

Informations de copyright

© 2018 EAN.

Auteurs

C Bertolin (C)

Department of Neurosciences, University of Padova, Padova, Italy.

G Querin (G)

Laboratoire d'Imagerie Biomédicale, Sorbonne University, CNRS, INSERM, Paris, France.

I Martinelli (I)

Department of Neurosciences, University of Padova, Padova, Italy.

M Pennuto (M)

Department of Biomedical Sciences, University of Padova, Padova, Italy.
Venetian Institute of Molecular Medicine, Padova, Italy.
Myology Center, University of Padova, Padova, Italy.
Padova Neuroscience Center, Padova, Italy.

E Pegoraro (E)

Department of Neurosciences, University of Padova, Padova, Italy.

G Sorarù (G)

Department of Neurosciences, University of Padova, Padova, Italy.

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