High frequency of intermediary alleles in the HTT gene in Northern Sweden - The Swedish Huntingtin Alleles and Phenotype (SHAPE) study

Jimmy Sundblom,Maria Ghazarian,Stefan Söderberg,Jan-Håkan Jansson,Ann-Sofi Strand,Ingvar A Bergdahl,Eva-Lena Stattin,Valter Niemelä

doi:10.1038/s41598-020-66643-0

Jimmy Sundblom, Maria Ghazarian + Show 6 more

Open Access

https://doi.org/10.1038/s41598-020-66643-0

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Abstract

Trinucleotide (CAG) repeat expansions longer than 39 in the huntingtin (HTT) gene cause Huntington’s disease (HD). The frequency of intermediate alleles (IA) with a length of 27–35 in the general population is not fully known, but studied in specific materials connected to the incidence of HD. The Swedish Huntingtin Alleles and Phenotype (SHAPE) study aims to assess the frequency of trinucleotide repeat expansions in the HTT gene in north Sweden. 8260 individuals unselected for HD from the counties of Norr- and Västerbotten in the north of Sweden were included. DNA samples were obtained and analysis of the HTT gene was performed, yielding data on HTT gene expansion length in 7379 individuals. A high frequency of intermediate alleles, 6.8%, was seen. Also, individuals with repeat numbers lower than ever previously reported (<5) were found. These results suggest a high frequency of HD in the norther parts of Sweden. Subsequent analyses may elucidate the influence of IA:s on traits other than HD.

Highlights

The worldwide prevalence of Huntington’s disease (HD) is 5.5/100 0006, making it a relatively common monogenic neurological disorder
The aim of this study is to describe the frequency of different CAG expansion lengths in the HTT gene in a population not selected for familial history of HD
Northern Sweden Health and Disease Study (NSHDS) includes individuals recruited from three large epidemiology projects; the Västerbotten Intervention Project (VIP)[22], the Northern Sweden MONItoring of Trends and Determinants in Cardiovascular Diseases project (MONICA)[23], and the Mammary Screening Program (MSP)[21]

Summary

Introduction

The worldwide prevalence of HD is 5.5/100 0006, making it a relatively common monogenic neurological disorder. Rare cases have been reported where the classical phenotype has presented in individuals with repeat expansion numbers in the intermediate interval[9,10]. As commercial genetic screening tests are gaining use outside of the healthcare provider setting, it may be a question of time before the HTT gene (along with other monogenic disorders) is included in such panels. This would pose new demands on the healthcare providers to manage patients with genetic test results acquired without any family history of HD17

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