Mitchell Elyse, Douglas Andrew, Kjaegaard Susanne, Callewaert Bert, Vanlander Arnaud, Janssens Sandra, Yuen Amy Lawson, Skinner Cindy, Failla Pinella, Alberti Antonino, Avola Emanuela, Fichera Marco, Kibaek Maria, Digilio Maria C, Hannibal Mark C, den Hollander Nicolette S, Bizzarri Veronica, Renieri Alessandra, Mencarelli Maria Antonietta, Fitzgerald Tomas, Piazzolla Serena, van Oudenhove Elke, Romano Corrado, Schwartz Charles, Eichler Evan E, Slavotinek Anne, Escobar Luis, Rajan Diana, Crolla John, Carter Nigel, Hodge Jennelle C, Mefford Heather C
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Princess Anne Hospital, Wessex Clinical Genetics Service, Southhampton, United Kingdom.
Am J Med Genet A. 2015 Dec;167A(12):3038-45. doi: 10.1002/ajmg.a.37351. Epub 2015 Sep 30.
The ability to identify the clinical nature of the recurrent duplication of chromosome 17q12 has been limited by its rarity and the diverse range of phenotypes associated with this genomic change. In order to further define the clinical features of affected patients, detailed clinical information was collected in the largest series to date (30 patients and 2 of their siblings) through a multi-institutional collaborative effort. The majority of patients presented with developmental delays varying from mild to severe. Though dysmorphic features were commonly reported, patients do not have consistent and recognizable features. Cardiac, ophthalmologic, growth, behavioral, and other abnormalities were each present in a subset of patients. The newly associated features potentially resulting from 17q12 duplication include height and weight above the 95th percentile, cataracts, microphthalmia, coloboma, astigmatism, tracheomalacia, cutaneous mosaicism, pectus excavatum, scoliosis, hypermobility, hypospadias, diverticulum of Kommerell, pyloric stenosis, and pseudohypoparathryoidism. The majority of duplications were inherited with some carrier parents reporting learning disabilities or microcephaly. We identified additional, potentially contributory copy number changes in a subset of patients, including one patient each with 16p11.2 deletion and 15q13.3 deletion. Our data further define and expand the clinical spectrum associated with duplications of 17q12 and provide support for the role of genomic modifiers contributing to phenotypic variability.
17q12染色体重复的罕见性以及与这种基因组变化相关的多种表型，限制了人们识别其临床性质的能力。为了进一步明确受影响患者的临床特征，通过多机构合作，在迄今为止最大的系列研究（30名患者及其2名兄弟姐妹）中收集了详细的临床信息。大多数患者存在从轻度到重度不等的发育迟缓。虽然常见有畸形特征的报告，但患者并没有一致且可识别的特征。心脏、眼科、生长、行为及其他异常在部分患者中均有出现。17q12重复可能新出现的相关特征包括身高和体重高于第95百分位数、白内障、小眼症、缺损、散光、气管软化、皮肤镶嵌现象、漏斗胸、脊柱侧弯、关节活动过度、尿道下裂、Kommerell憩室、幽门狭窄和假性甲状旁腺功能减退。大多数重复是遗传而来的，一些携带者父母报告有学习障碍或小头畸形。我们在部分患者中发现了其他可能有影响的拷贝数变化，包括1名患者有16p11.2缺失，另1名患者有15q13.3缺失。我们的数据进一步明确并扩展了与17q12重复相关的临床谱，并为基因组修饰因子在表型变异中的作用提供了支持。
