Long-read sequence analysis of the MECP2 gene in Rett syndrome patients:: correlation of disease severity with mutation type and location
Long-read sequence analysis of the MECP2 gene in Rett syndrome patients:: correlation of disease severity with mutation type and location
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DOI：
10.1093/hmg/9.7.1119
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发表时间：
2000-04-12
影响因子：
3.5
通讯作者：
Clarke, A
中科院分区：
文献类型：
--
作者：
Cheadle, JP;Gill, H;Clarke, A
甲基- cpg结合蛋白基因MECP2在Xq28位点的突变导致Rett综合征（RTT），这是一种x连锁的显性神经发育障碍，其特征是年轻女孩发育的停滞期和退行期。在48例经典散发性RTT女性、7例可能的家族性RTT家族和5例散发性RTT女性中发现了MECP2突变，这些女性具有提示但不能诊断为RTT的特征。对所有病例的MECP2基因编码区进行了长距离PCR和长读直接测序，发现44/55（80%）无亲缘关系的经典散发性和家族性RTT患者中存在突变，但只有1/5（20%）具有提示但非诊断性RTT的散发性病例中存在突变，共发现21种不同的突变（12种错义突变，4种无义突变，5种移帧突变）；其中14项是新的。所有错义突变都位于甲基cpg结合域或转录抑制域，在33例不相关的病例中有9个复发突变（占MECP2突变病例的73%）。与截断突变患者相比，携带错义突变患者的疾病明显较轻（P = 0.0023），与早期截断突变相比，较轻的疾病与晚期相关（P = 0.0190）。
Mutations in the methyl-CpG-binding protein gene MECP2 at Xq28 cause Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder characterized by a period of stagnation followed by regression in the development of young girls, Mutations were sought in MECP2 in 48 females with classical sporadic RTT, seven families with possible familial RTT and five sporadic females with features suggestive, but not diagnostic of RTT, Long distance PCR coupled with long-read direct sequencing was employed to sequence the entire MECP2 gene coding region in all cases, Mutations were identified in 44/55 (80%) unrelated classical sporadic and familial RTT patients, but only 1/5 (20%) sporadic cases with suggestive but non-diagnostic features of RTT, Twenty-one different mutations were identified (12 missense, four nonsense and five frame-shift mutations); 14 of these were novel. All missense mutations were located either in the methyl-CpG-binding domain or in the transcription repression domain, Nine recurrent mutations were characterized in a total of 33 unrelated cases (73% of all cases with MECP2 mutations). Significantly milder disease was noted in patients carrying missense mutations as compared with those with truncating mutations (P = 0.0023), and milder disease was associated with late as compared with early truncating mutations (P = 0.0190).