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Transmission of C9orf72 hexanucleotide repeat expansions in sporadic amyotrophic lateral sclerosis: an Australian trio study. | LitMetric
Abnormally expanded C9orf72 hexanucleotide repeats are found in up to 7% of patients with sporadic amyotrophic lateral sclerosis (SALS). It is not known whether the sporadic nature of the disease represents incomplete penetrance of the phenotype or expansion of the repeat in the SALS patient. The sizes of C9orf72 hexanucleotide repeats were measured in blood DNA of 43 SALS patients and their parents who had no symptoms of ALS. Two SALS patients (4.7%) had abnormally expanded (>30 repeats) C9orf72 repeats. Both of their fathers (one with dementia) also had abnormally expanded repeats. Nine SALS patients had intermediate-normal repeat sizes (7-30 repeats); in each of these, one parent had a similar repeat size. In the remaining 32 SALS patients, the repeat sizes were low-normal (<7 repeats). There was no evidence of repeat instability leading to abnormal numbers of repeats in any SALS patient in this trio cohort. Our results suggest that a simple monogenic mechanism is not likely to be the cause of C9orf72 repeat-related SALS.
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