Castillo Angela, Kramer Nancy, Schwartz Charles E, Miles Judith H, DuPont Barbara R, Rosenfeld Jill A, Graham John M
Medical Genetics Institute, Cedars Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles CA, USA.
Greenwood Genetic Center, Greenwood SC, USA.
Eur J Med Genet. 2014 Nov-Dec;57(11-12):654-8. doi: 10.1016/j.ejmg.2014.08.009. Epub 2014 Sep 16.
A previous report described a unique phenotype associated with an apparently de novo 732 kb 19q13.32 microdeletion, consisting of intellectual disability, facial asymmetry, ptosis, oculomotor abnormalities, orofacial clefts, cardiac defects, scoliosis and chronic constipation. We report three unrelated patients with developmental delay and dysmorphic features, who were all found to have interstitial 19q13.32 microdeletions of varying sizes. Both the previously reported patient and our Patient 1 with a larger, 1.3-Mb deletion have distinctive dysmorphic features and medical problems, allowing us to define a recognizable 19q13.32 microdeletion syndrome. Patient 1 was hypotonic and dysmorphic at birth, with aplasia of the posterior corpus callosum, bilateral ptosis, oculomotor paralysis, down-slanting palpebral fissures, facial asymmetry, submucosal cleft palate, micrognathia, wide-spaced nipples, right-sided aortic arch, hypospadias, bilateral inguinal hernias, double toenail of the left second toe, partial 2-3 toe syndactyly, kyphoscoliosis and colonic atony. Therefore, the common features of the 19q13.32 microdeletion syndrome include facial asymmetry, ptosis, oculomotor paralysis, orofacial clefting, micrognathia, kyphoscoliosis, aortic defects and colonic atony. These findings are probably related to a deletion of some combination of the 20-23 genes in common between these two patients, especially NPAS1, NAPA, ARHGAP35, SLC8A2, DHX34, MEIS3, and ZNF541. These candidate genes are expressed in the brain parenchyma, glia, heart, gastrointestinal tract and musculoskeletal system and likely play a fundamental role in the expression of this phenotype. This report delineates the phenotypic spectrum associated with the haploinsufficiency of genes found in 19q13.32.
先前的一份报告描述了一种与新发的732 kb 19q13.32微缺失相关的独特表型，包括智力残疾、面部不对称、上睑下垂、眼球运动异常、口面裂、心脏缺陷、脊柱侧凸和慢性便秘。我们报告了3例发育迟缓且有畸形特征的无关患者，他们均被发现存在不同大小的19q13.32间质性微缺失。先前报告的患者以及我们的患者1（有一个更大的1.3 Mb缺失）均有独特的畸形特征和医学问题，这使我们能够定义一种可识别的19q13.32微缺失综合征。患者1出生时肌张力减退且有畸形，胼胝体后部发育不全、双侧上睑下垂、眼球运动麻痹、睑裂向下倾斜、面部不对称、黏膜下腭裂、小颌畸形、乳头间距宽、右侧主动脉弓、尿道下裂、双侧腹股沟疝、左第二趾双趾甲、2 - 3趾部分并趾、脊柱后凸侧弯和结肠无张力。因此，19q13.32微缺失综合征的共同特征包括面部不对称、上睑下垂、眼球运动麻痹、口面裂、小颌畸形、脊柱后凸侧弯、主动脉缺陷和结肠无张力。这些发现可能与这两名患者共有的20 - 23个基因的某些组合缺失有关，尤其是NPAS1、NAPA、ARHGAP35、SLC8A2、DHX34、MEIS3和ZNF541。这些候选基因在脑实质、神经胶质、心脏、胃肠道和肌肉骨骼系统中表达，可能在该表型的表达中起重要作用。本报告描述了与19q。13.32中发现的基因单倍剂量不足相关的表型谱。
