Small supernumerary marker chromosomes (SMCs): genotype-phenotype correlation and classification
Small supernumerary marker chromosomes (SMCs): genotype-phenotype correlation and classification
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DOI：
10.1007/s00439-003-1016-3
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发表时间：
2003-12-01
期刊：
影响因子：
5.3
通讯作者：
Liehr, T
中科院分区：
文献类型：
--
作者：
Starke, H;Nietzel, A;Liehr, T
小额外标记染色体（SMC）存在于约0.05%的人类群体中。在大约30%的SMC携带者中（不包括类似于60%的来自一条近端着丝粒染色体的SMC），观察到异常表型。SMC的临床结果难以预测，因为它们可能具有不同的表型结果，这是由于（1）常染色质DNA含量的差异，（2）不同程度的嵌合现象，和/或（3）与SMC同源的染色体的单亲二体性（UPD）。在这里，我们提出了35个SMC，这是来自所有人类染色体，除了染色体6，证明了适当的分子细胞遗传学方法，如着丝粒特异性荧光原位杂交（cenM-FISH），荧光显带（MCB），和亚着丝粒特异性荧光原位杂交（subcenM-FISH）。在9例没有异常表型的病例中，既没有部分近端三体也没有UPD。异常的临床结果，如精神运动迟缓和/或颅面畸形，与7例亚着丝粒单拷贝探针被证明存在于三个副本。相反，在8例正常表型的病例中，近端常染色体物质被检测为部分三体。在12例病例中研究了UPD，随后在两例SMC病例中检测到UPD（部分UPD 4p和der（22）综合征患者的母体UPD 22），表明SMC携带者患UPD的风险增加。目前，1 p、1 q、2 p、6p、6 q、7 q、9 p和12 q的小近端三体似乎导致临床表现，而2 q、3 p、3q、5 q、7 p、8 p、17 p和18 p的部分近端三体可能与显著的临床症状无关。关于临床结果，SMCs的分类，建议考虑分子遗传学和分子细胞遗传学特征，目前可用的方法证明。
Small supernumerary marker chromosomes (SMCs) are present in about 0.05% of the human population. In approximately 30% of SMC carriers (excluding the similar to60% SMC derived from one of the acrocentric chromosomes), an abnormal phenotype is observed. The clinical outcome of an SMC is difficult to predict as they can have different phenotypic consequences because of (1) differences in euchromatic DNA-content, (2) different degrees of mosaicism, and/or (3) uniparental disomy (UPD) of the chromosomes homologous to the SMC. Here, we present 35 SMCs, which are derived from all human chromosomes, apart from chromosome 6, as demonstrated by the appropriate molecular cytogenetic approaches, such as centromere-specific multicolor fluoresence in situ hybridization (cenM-FISH), multicolor banding (MCB), and subcentromere-specific multicolor FISH (subcenM-FISH). In nine cases without an aberrant phenotype, neither partial proximal trisomies nor UPD could be detected. Abnormal clinical findings, such as psychomotoric retardation and/or craniofacial dysmorphisms, were associated with seven of the cases in which subcentromeric single-copy probes were proven to be present in three copies. Conversely, in eight cases with a normal phenotype, proximal euchromatic material was detected as partial trisomy. UPD was studied in 12 cases and subsequently detected in two of the cases with SMC (partial UPD 4p and maternal UPD 22 in a der(22)-syndrome patient), indicating that SMC carriers have an enhanced risk for UPD. At present, small proximal trisomies of 1p, 1q, 2p, 6p, 6q, 7q, 9p, and 12q seem to lead to clinical manifestations, whereas partial proximal trisomies of 2q, 3p, 3q, 5q, 7p, 8p, 17p, and 18p may not be associated with significant clinical symptoms. With respect to clinical outcome, a classification of SMCs is proposed that considers molecular genetic and molecular cytogenetic characteristics as demonstrated by presently available methods.