Selmer Kaja K, Bryne Einar, Rødningen Olaug K, Fannemel Madeleine
Department of Medical Genetics, Oslo University Hospital, Postboks 4956 Nydalen, 0424 Oslo, Norway.
Eur J Med Genet. 2012 Dec;55(12):715-8. doi: 10.1016/j.ejmg.2012.08.005. Epub 2012 Aug 23.
The 1q44 deletion syndrome has shown to be a recognizable phenotype with developmental delay, short stature and corpus callosum abnormalities as relatively consistent features. However, the disorder is still clinically heterogeneous and a genotype-phenotype correlation has been challenging to establish. In particular, a delineation of a critical region for the corpus callosum development has turned out to be difficult, and many candidate genes have been proposed. We present here a patient boy with a clinical picture of the 1q44 deletion syndrome, including a thin corpus callosum, and a small de novo 1q44 deletion. The deletion spans a maximum of 163 kb, a region which only contains the two genes FAM36A and HNRNPU. This finding supports the previously suggested hypothesis that the HNRNPU is an essential gene to the development of corpus callosum. However, as patients with deletions outside this interval also have been reported to have corpus callosum abnormalities, other mechanisms are probably also involved. We also identified two conserved non-coding regions in the deleted region of the patient, and speculate that also other elements interfere with the complex interplay and spatiotemporal gene expression during embryonic development.
1q44缺失综合征已被证明是一种具有可识别表型的疾病，发育迟缓、身材矮小和胼胝体异常是相对一致的特征。然而，该疾病在临床上仍具有异质性，建立基因型-表型相关性一直具有挑战性。特别是，确定胼胝体发育的关键区域一直很困难，并且已经提出了许多候选基因。我们在此报告一名患有1q44缺失综合征临床表现的男童，包括胼胝体变薄，以及一个小的新发1q44缺失。该缺失最大跨度为163 kb，该区域仅包含两个基因FAM36A和HNRNPU。这一发现支持了先前提出的假设，即HNRNPU是胼胝体发育的必需基因。然而，由于据报道在此区间外发生缺失的患者也有胼胝体异常，可能还涉及其他机制。我们还在患者的缺失区域中鉴定出两个保守的非编码区域，并推测在胚胎发育过程中还有其他因素干扰了复杂的相互作用和时空基因表达。
