Department of Neurology, ALS Unit, Instituto de Investigación Biomédica Hospital 12 de Octubre, Madrid, Spain.
Hum Mutat. 2013 Jan;34(1):79-82. doi: 10.1002/humu.22211. Epub 2012 Oct 11.
A hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) can cause amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD). We assessed its frequency in 781 sporadic ALS (sALS) and 155 familial ALS (fALS) cases, and in 248 Spanish controls. We tested the presence of the reported founder haplotype among mutation carriers and in 171 Ceph Europeans from Utah (CEU), 170 Yoruba Africans, 81 Han Chinese, and 85 Japanese subjects. The C9orf72 expansion was present in 27.1% of fALS and 3.2% of sALS. Mutation carriers showed lower age at onset (P = 0.04), shorter survival (P = 0.02), greater co-occurrence of FTD (P = 8.2 × 10(-5)), and more family history of ALS (P = 1.4 × 10(-20)), than noncarriers. No association between alleles within the normal range and the risk of ALS was found (P = 0.12). All 61 of the mutation carriers were tested and a patient carrying 28 hexanucleotide repeats presented with the founder haplotype. This haplotype was found in 5.6% Yoruba Africans, 8.9% CEU, 3.9% Japanese, and 1.6% Han Chinese chromosomes.
9 号染色体开放阅读框 72（C9orf72）的六核苷酸重复扩展可导致肌萎缩侧索硬化症（ALS）和/或额颞叶痴呆（FTD）。我们评估了其在 781 例散发性 ALS（sALS）和 155 例家族性 ALS（fALS）病例以及 248 名西班牙对照中的频率。我们在突变携带者中以及在来自犹他州的 171 名 CEph 欧洲人（CEU）、170 名约鲁巴非洲人、81 名汉族人和 85 名日本人中测试了报道的起始单倍型的存在。C9orf72 扩展存在于 27.1%的 fALS 和 3.2%的 sALS 中。突变携带者的发病年龄更低（P = 0.04），生存时间更短（P = 0.02），FTD 共病发生率更高（P = 8.2×10(-5)），ALS 家族史更多（P = 1.4×10(-20)），而非携带者。在正常范围内的等位基因与 ALS 风险之间未发现关联（P = 0.12）。对 61 名突变携带者进行了测试，一名携带 28 个六核苷酸重复的患者携带起始单倍型。该单倍型在 5.6%的约鲁巴非洲人、8.9%的 CEU、3.9%的日本人以及 1.6%的汉族人中存在。
