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Neurology. 2013 Jan 22;80(4):366-70. doi: 10.1212/WNL.0b013e31827f08ea. Epub 2013 Jan 2.

C9ORF72 hexanucleotide expansions of 20-22 repeats are associated with frontotemporal deterioration.

Author information

1
Department of Neurology, Fundación Jiménez Díaz, Madrid, Spain. egomezt@fjd.es

Abstract

OBJECTIVE:

Expansions of more than 30 hexanucleotide repetitions in the C9ORF72 gene are a common cause of frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS). However, the range of 20-30 repetitions is rarely found and still has unclear significance. A screening of our cohort of cases with FTD (n = 109) revealed 4 mutation carriers (>30 repetitions) but also 5 probands with 20-22 confirmed repetitions. This study explored the possible pathogenic correlation of the 20-22 repeats expansion (short expansion).

METHODS:

Comparison of clinical phenotypes between cases with long vs short expansions; search for segregation in the families of probands with short expansion; analysis of the presence of the common founder haplotype, described for expansions >30 repeats, in the cases having the short expansion; and analysis of the distribution of hexanucleotide repeat alleles in a control population.

RESULTS:

No different patterns were found in the clinical phenotype or aggressiveness of the disease when comparing cases with long or short expansions. Cases in both groups had psychiatric symptoms during 1-3 decades before evolving insidiously to cognitive deterioration. The study of the families with short expansion showed clear segregation of the 20-22 repeats allele with the disease. Moreover, this 20-22 repeats allele was associated in all cases with the pathogenic founder haplotype. None of 216 controls had alleles with more than 14 repetitions.

CONCLUSIONS:

Description of these families suggests that short C9ORF72 hexanucleotide expansions are also related to frontotemporal cognitive deterioration.

PMID:
23284068
DOI:
10.1212/WNL.0b013e31827f08ea
[Indexed for MEDLINE]

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