Molecular analysis of ring chromosome 20 syndrome reveals two distinct groups of patients
Molecular analysis of ring chromosome 20 syndrome reveals two distinct groups of patients
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DOI：
10.1136/jmg.2010.080382
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发表时间：
2011-01-01
影响因子：
4
通讯作者：
Spinner, Nancy B.
中科院分区：
文献类型：
--
作者：
Conlin, Laura K.;Kramer, Whitney;Spinner, Nancy B.
研究背景20号环状染色体综合征（R20）是一种罕见的遗传性疾病，与难治性电临床癫痫综合征及智力障碍和畸形并存，为了解20号环状染色体（r（20））的结构和组成，对28例患者的血液标本进行了细胞遗传学、荧光原位杂交、和/或高分辨率全基因组单核苷酸多态性阵列分析。第1组（N21）为r（20）嵌合体，为正常细胞系，两个细胞系均未检测到20号染色体的缺失或重复。这些环的镶嵌性质表明了合子后起源，通过端粒区域的融合形成环，而没有明显的亚端粒或端粒DNA的丢失。第2组（N7）为非嵌合环状染色体，在染色体一端或两端靠近环状融合点处缺失。这些环的非马赛克性质与减数分裂起源一致。非马赛克患者（第2组，中位发作年龄2.1岁）的癫痫发作年龄显著低于马赛克患者（第1组，中位发作年龄6.0岁）。从组2的患者有更广泛的comorbidity.Conclusions这些研究表明，r（20）是分子异质性和形成两个不同的机制，这反过来又产生不同的表型谱。
Background The ring chromosome 20 syndrome (R20) is a rare genetic disorder associated with a refractory electroclinical epilepsy syndrome and variably expressed comorbidities of intellectual disability and dysmorphism.Methods To understand the structure and composition of the ring chromosome 20 (r(20)) in this patient cohort, blood specimens from 28 affected individuals were analysed by cytogenetic, fluorescence in situ hybridisation, and/or high resolution whole genome single nucleotide polymorphism array analysis.Results These studies revealed two distinct groups of patients. Group 1 (N 21) was mosaic for the r(20) and a normal cell line with no detectable deletions or duplications of chromosome 20 in either cell line. The mosaic nature of these rings suggests a postzygotic origin with formation of the ring by fusion of the telomeric regions with no apparent loss of subtelomeric or telomeric DNA. Group 2 (N 7) had non-mosaic ring chromosomes with a deletion at one or both ends of the chromosome, near the ring fusion point. The non- mosaic nature of these rings is consistent with a meiotic origin. The age of onset of seizures was significantly lower in the non- mosaic patients (group 2, median age of onset 2.1 years) than in the mosaic patients (group 1, median age of onset 6.0 years). Patients from group 2 had more extensive comorbidities.Conclusions These studies demonstrate that r(20) is molecularly heterogeneous and formed by two distinct mechanisms, which, in turn, produce different phenotypic spectrums.