McMichael Gai, Girirajan Santhosh, Moreno-De-Luca Andres, Gecz Jozef, Shard Chloe, Nguyen Lam Son, Nicholl Jillian, Gibson Catherine, Haan Eric, Eichler Evan, Martin Christa Lese, MacLennan Alastair
Robinson Institute, The University of Adelaide, Adelaide, South Australia, Australia.
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Eur J Hum Genet. 2014 Jan;22(1):40-5. doi: 10.1038/ejhg.2013.93. Epub 2013 May 22.
Recent studies have established the role of rare copy number variants (CNVs) in several neurological disorders but the contribution of rare CNVs to cerebral palsy (CP) is not known. Fifty Caucasian families having children with CP were studied using two microarray designs. Potentially pathogenic, rare (<1% population frequency) CNVs were identified, and their frequency determined, by comparing the CNVs found in cases with 8329 adult controls with no known neurological disorders. Ten of the 50 cases (20%) had rare CNVs of potential relevance to CP; there were a total of 14 CNVs, which were observed in <0.1% (<8/8329) of the control population. Eight inherited from an unaffected mother: a 751-kb deletion including FSCB, a 1.5-Mb duplication of 7q21.13, a 534-kb duplication of 15q11.2, a 446-kb duplication including CTNND2, a 219-kb duplication including MCPH1, a 169-kb duplication of 22q13.33, a 64-kb duplication of MC2R, and a 135-bp exonic deletion of SLC06A1. Three inherited from an unaffected father: a 386-kb deletion of 12p12.2-p12.1, a 234-kb duplication of 10q26.13, and a 4-kb exonic deletion of COPS3. The inheritance was unknown for three CNVs: a 157-bp exonic deletion of ACOX1, a 693-kb duplication of 17q25.3, and a 265-kb duplication of DAAM1. This is the first systematic study of CNVs in CP, and although it did not identify de novo mutations, has shown inherited, rare CNVs involving potentially pathogenic genes and pathways requiring further investigation.
近期研究已确定罕见拷贝数变异（CNV）在多种神经系统疾病中的作用，但罕见CNV对脑瘫（CP）的影响尚不清楚。我们使用两种微阵列设计对50个有患CP儿童的白种人家庭进行了研究。通过比较50例患儿与8329名无已知神经系统疾病的成年对照中发现的CNV，确定了潜在致病性罕见（人群频率<1%）CNV，并测定了其频率。50例患儿中有10例（20%）存在与CP可能相关的罕见CNV；共有14个CNV，在对照人群中观察到的频率<0.1%（<8/8329）。8个从未受影响的母亲遗传而来：一个包含FSCB的751 kb缺失、7q21.13的1.5 Mb重复、15q11.2的534 kb重复、一个包含CTNND2的446 kb重复、一个包含MCPH1的219 kb重复、22q13.33的169 kb重复、MC2R的64 kb重复以及SLC06A1的135 bp外显子缺失。3个从未受影响的父亲遗传而来：12p12.2 - p12.1的386 kb缺失、10q26.13的234 kb重复以及COPS3的4 kb外显子缺失。3个CNV的遗传情况未知：ACOX1的157 bp外显子缺失、17q25.3的693 kb重复以及DAAM1的265 kb重复。这是对CP中CNV的首次系统性研究，虽然未发现新发突变，但已显示存在涉及潜在致病基因和途径的遗传性罕见CNV，需要进一步研究。
