Departement de Génétique et INSERM U781, Université Paris Descartes, Hôpital Necker Enfants-Malades, Paris, France.
Eur J Hum Genet. 2010 Feb;18(2):227-32. doi: 10.1038/ejhg.2009.162. Epub 2009 Oct 21.
Overgrowth syndromes are a heterogeneous group of conditions including endocrine hormone disorders, several genetic syndromes and other disorders with unknown etiopathogenesis. Among genetic causes, chromosomal deletions and duplications such as dup(4)(p16.3), dup(15)(q26qter), del(9)(q22.32q22.33), del(22)(q13) and del(5)(q35) have been identified in patients with overgrowth. Most of them, however, remain undetectable using banding karyotype analysis. In this study, we report on the analysis using a 1-Mb resolution array-based comparative genomic hybridization (CGH) of 93 patients with either a recognizable overgrowth condition (ie, Sotos syndrome or Weaver syndrome) or an unclassified overgrowth syndrome. Five clinically relevant imbalances (three duplications and two deletions) were identified and the pathogenicity of two additional anomalies (one duplication and one deletion) is discussed. Altered segments ranged in size from 0.32 to 18.2 Mb, and no recurrent abnormality was identified. These results show that array-CGH provides a high diagnostic yield in patients with overgrowth syndromes and point to novel chromosomal regions associated with these conditions. Although chromosomal deletions are usually associated with growth retardation, we found that the majority of the imbalances detected in our patients are duplications. Besides their importance for diagnosis and genetic counseling, our results may allow to delineate new contiguous gene syndromes associated with overgrowth, pointing to new genes, the deregulation of which may be responsible for growth defect.
过度生长综合征是一组异质性疾病，包括内分泌激素紊乱、几种遗传综合征和其他病因不明的疾病。在遗传原因中，已在过度生长的患者中发现了染色体缺失和重复，如 dup(4)(p16.3)、dup(15)(q26qter)、del(9)(q22.32q22.33)、del(22)(q13)和 del(5)(q35)。然而，大多数情况下，使用带型核型分析仍无法检测到。在这项研究中，我们报告了对 93 名患者进行 1-Mb 分辨率基于阵列的比较基因组杂交 (CGH) 的分析，这些患者要么存在可识别的过度生长情况（即 Sotos 综合征或 Weaver 综合征），要么存在未分类的过度生长综合征。确定了五个具有临床意义的不平衡（三个重复和两个缺失），并讨论了另外两个异常（一个重复和一个缺失）的致病性。改变的片段大小从 0.32 到 18.2 Mb 不等，未发现重复异常。这些结果表明，阵列-CGH 在过度生长综合征患者中提供了高诊断率，并指出了与这些疾病相关的新的染色体区域。尽管染色体缺失通常与生长迟缓有关，但我们发现我们患者中检测到的大多数不平衡是重复。除了对诊断和遗传咨询很重要外，我们的结果还可能划定与过度生长相关的新的连续基因综合征，指出新的基因，其失调可能是生长缺陷的原因。
