Thapa Monika, Asamoah Alexander, Gowans Gordon C, Platky Kathryn C, Barch Margaret J, Mouchrani Patricia, Rajakaruna Cecilia, Hersh Joseph H
WCEC Cytogenetic Laboratory, Department of Pediatrics, University of Louisville, Louisville, Kentucky.
Am J Med Genet A. 2014 Apr;164A(4):1069-74. doi: 10.1002/ajmg.a.36396. Epub 2014 Jan 23.
Pure/direct duplications on the long arm of chromosome 4 represent an infrequent chromosomal finding. Description of clinical findings in 30 patients has resulted in defining the 4q-associated phenotype. However, such duplications have not been molecularly or genomically characterized yet, limiting genotype-phenotype correlation. We report on the first two patients with a duplication involving the distal third of 4q that are characterized molecularly and genomically. Clinical features in our patients typical of 4q duplication syndrome included mild intellectual disability, cranial malformation, minor facial dysmorphism, and digital anomaly. Duplication of the segment 4q33-4q34, appears to be the critical region resulting in the phenotype associated with 4q duplication syndrome. The genes GLRA3, GMP6A that are invovled in neurogenesis and HAND2 in craniofacial development, within the duplicated region of 4q, may play a key role in the clinical phenotype. As more reporting on molecular characterization of 4q duplication becomes available, the role of these underlying genes may become clearer.
4号染色体长臂上的纯合/直接重复是一种罕见的染色体发现。对30例患者临床发现的描述已确定了与4q相关的表型。然而，此类重复尚未进行分子或基因组特征分析，限制了基因型与表型的相关性。我们报告了首例两例涉及4q远端三分之一区域重复的患者，并对其进行了分子和基因组特征分析。我们患者中典型的4q重复综合征临床特征包括轻度智力残疾、颅骨畸形、轻微面部畸形和手指异常。4q33 - 4q34片段的重复似乎是导致与4q重复综合征相关表型的关键区域。在4q重复区域内，参与神经发生的GLRA3、GMP6A基因以及参与颅面发育的HAND2基因可能在临床表型中起关键作用。随着更多关于4q重复分子特征的报告出现，这些潜在基因的作用可能会更加明确。
