Copy-number variations on the X chromosome in Japanese patients with mental retardation detected by array-based comparative genomic hybridization analysis
Copy-number variations on the X chromosome in Japanese patients with mental retardation detected by array-based comparative genomic hybridization analysis
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DOI：
10.1038/jhg.2010.74
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发表时间：
2010-09-01
影响因子：
3.5
通讯作者：
Inazawa, Johji
中科院分区：
文献类型：
--
作者：
Honda, Shozo;Hayashi, Shin;Inazawa, Johji
X连锁精神发育迟滞（XLMR）是一种常见的、临床上复杂的、遗传异质性的疾病，其起源于X染色体沿着的许多突变。虽然在过去十年的研究已经确定了超过90个XLMR基因，但仍有更多的基因尚未确定。在这项研究中，拷贝数变异（CNVs）的筛选与MR的个人从144个家庭的阵列为基础的比较基因组杂交（aCGH）使用细菌人工染色体为基础的X-tiling阵列。在10个家系（6.9%）中检测到候选致病性CNVs（pCNVs）。其中5个家系的pCNVs涉及已知的XLMR基因，3个家系的Xq 28含有MECP 2的重复，1个家系的Xp11.22-p11.23含有FTSJ 1和PQBP 1的重复，1个家系的Xp11.22含有SHROOM 4缺失。在5个家系中检测到新的候选pCNVs：2个无关家系中检测到dup（X）（p22.2）和dup（X）（p21.3）中含有部分REPS 2、NHS和IL 1 RAPL 1的相同复合体pCNVs; 1个家系中检测到Xp22.2中含有部分FRMPD 4的重复序列;在6个和3个家庭中分别获得了父母和母亲的样本，并且pCNVs从这些家庭中的每个母亲那里遗传，而不是先证者的家庭中缺失SHROOM 4。本研究将有助于发现新的XLMR基因和导致MR的机制，并揭示XLMR的临床条件和基因组背景。Journal of Human Genetics（2010）55，590-599; doi：10.1038/jhg.2010.74; 2010年7月8日在线发表
X-linked mental retardation (XLMR) is a common, clinically complex and genetically heterogeneous disease arising from many mutations along the X chromosome. Although research during the past decade has identified >90 XLMR genes, many more remain uncharacterized. In this study, copy-number variations (CNVs) were screened in individuals with MR from 144 families by array-based comparative genomic hybridization (aCGH) using a bacterial artificial chromosome-based X-tiling array. Candidate pathogenic CNVs (pCNVs) were detected in 10 families (6.9%). Five of the families had pCNVs involving known XLMR genes, duplication of Xq28 containing MECP2 in three families, duplication of Xp11.22-p11.23 containing FTSJ1 and PQBP1 in one family, and deletion of Xp11.22 bearing SHROOM4 in one family. New candidate pCNVs were detected in five families as follows: identical complex pCNVs involved in dup(X)(p22.2) and dup(X)(p21.3) containing part of REPS2, NHS and IL1RAPL1 in two unrelated families, duplication of Xp22.2 including part of FRMPD4, duplication of Xq21.1 including HDX and deletion of Xq24 noncoding region in one family, respectively. Both parents and only mother samples were available in six and three families, respectively, and pCNVs were inherited from each of their mothers in those families other than a family of the proband with deletion of SHROOM4. This study should help to identify the novel XLMR genes and mechanisms leading to MR and reveal the clinical conditions and genomic background of XLMR. Journal of Human Genetics (2010) 55, 590-599; doi:10.1038/jhg.2010.74; published online 8 July 2010