Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Eur J Hum Genet. 2010 Mar;18(3):278-84. doi: 10.1038/ejhg.2009.174. Epub 2009 Oct 21.
Deletions in chromosome 17q12 encompassing the HNF1 beta gene cause cystic renal disease and maturity onset diabetes of the young, and have been recently described as the first recurrent genomic deletion leading to diabetes. Earlier reports of patients with this microdeletion syndrome have suggested an absence of cognitive impairment, differentiating it from most other contiguous gene deletion syndromes. The reciprocal duplication of 17q12 is rare and has been hypothesized to be associated with an increased risk of epilepsy and mental retardation. We conducted a detailed clinical and molecular characterization of four patients with a deletion and five patients with a reciprocal duplication of this region. Our patients with deletion of 17q12 presented with cognitive impairment, cystic renal disease, seizures, and structural abnormalities of the brain. Patients with reciprocal duplications manifest with cognitive impairment and behavioral abnormalities, but not with seizures. Our findings expand the phenotypic spectrum associated with rearrangements of 17q12 and show that cognitive impairment is a part of the phenotype of individuals with deletions of 17q12.
染色体 17q12 缺失包括 HNF1β 基因导致囊性肾病和青少年起病的成年型糖尿病，最近被描述为导致糖尿病的首个复发性基因组缺失。先前报道的患有这种微缺失综合征的患者没有认知障碍，这将其与大多数其他连续基因缺失综合征区分开来。17q12 的反向重复是罕见的，据推测与癫痫和智力迟钝的风险增加有关。我们对四个患有缺失的患者和五个患有该区域反向重复的患者进行了详细的临床和分子特征分析。我们的 17q12 缺失患者表现出认知障碍、囊性肾病、癫痫发作和大脑结构异常。具有反向重复的患者表现出认知障碍和行为异常，但没有癫痫发作。我们的发现扩展了与 17q12 重排相关的表型谱，并表明认知障碍是 17q12 缺失个体表型的一部分。
