van Bon B W M, Koolen D A, Borgatti R, Magee A, Garcia-Minaur S, Rooms L, Reardon W, Zollino M, Bonaglia M C, De Gregori M, Novara F, Grasso R, Ciccone R, van Duyvenvoorde H A, Aalbers A M, Guerrini R, Fazzi E, Nillesen W M, McCullough S, Kant S G, Marcelis C L, Pfundt R, de Leeuw N, Smeets D, Sistermans E A, Wit J M, Hamel B C, Brunner H G, Kooy F, Zuffardi O, de Vries B B A
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
J Med Genet. 2008 Jun;45(6):346-54. doi: 10.1136/jmg.2007.055830. Epub 2008 Jan 4.
Patients with a microscopically visible deletion of the distal part of the long arm of chromosome 1 have a recognisable phenotype, including mental retardation, microcephaly, growth retardation, a distinct facial appearance and various midline defects including corpus callosum abnormalities, cardiac, gastro-oesophageal and urogenital defects, as well as various central nervous system anomalies. Patients with a submicroscopic, subtelomeric 1qter deletion have a similar phenotype, suggesting that the main phenotype of these patients is caused by haploinsufficiency of genes in this region.
To describe the clinical presentation of 13 new patients with a submicroscopic deletion of 1q43q44, of which nine were interstitial, and to report on the molecular characterisation of the deletion size.
The clinical presentation of these patients has clear similarities with previously reported cases with a terminal 1q deletion. Corpus callosum abnormalities were present in 10 of our patients. The AKT3 gene has been reported as an important candidate gene causing this abnormality. However, through detailed molecular analysis of the deletion sizes in our patient cohort, we were able to delineate the critical region for corpus callosum abnormalities to a 360 kb genomic segment which contains four possible candidate genes, but excluding the AKT3 gene.
1号染色体长臂远端出现显微镜下可见缺失的患者具有可识别的表型，包括智力发育迟缓、小头畸形、生长发育迟缓、独特的面部外观以及各种中线缺陷，包括胼胝体异常、心脏、胃食管和泌尿生殖系统缺陷，以及各种中枢神经系统异常。具有亚微观、亚端粒1qter缺失的患者具有相似的表型，这表明这些患者的主要表型是由该区域基因的单倍剂量不足引起的。
描述13例新的1q43q44亚微观缺失患者的临床表现，其中9例为间质缺失，并报告缺失大小的分子特征。
这些患者的临床表现与先前报道的末端1q缺失病例有明显相似之处。我们的患者中有10例存在胼胝体异常。AKT3基因已被报道为导致这种异常的重要候选基因。然而，通过对我们患者队列中缺失大小的详细分子分析，我们能够将胼胝体异常的关键区域划定为一个360 kb的基因组片段，该片段包含四个可能的候选基因，但不包括AKT3基因。
