Faguer Stanislas, Chassaing Nicolas, Bandin Flavio, Prouheze Cathie, Arveiler Benoît, Rooryck Caroline, Nogier Marie-Béatrice, Chauveau Dominique, Calvas Patrick, Decramer Stéphane
Nephrology and Immunology Department, University Hospital of Rangueil, Toulouse, France.
Eur J Med Genet. 2011 Jul-Aug;54(4):e437-40. doi: 10.1016/j.ejmg.2011.03.010. Epub 2011 Apr 19.
Chromosomal imbalance of the 17q12 region (which includes the HNF1B transcription factor) has recently emerged as a frequent condition. 17q12 deletion was found in patients with various renal abnormalities, diabetes mellitus (MODY type 5), genital tract or liver test abnormalities, while 17q12 duplication was identified in a subset of patients with autism, mental retardation, epilepsy and/or schizophrenia but no renal disorder. We report here two first-degree relatives carrying a 17q12 duplication and harboring various renal abnormalities (bilateral hypoplastic kidneys with vesico-ureteric reflux or multicystic dysplatic kidney with contralateral hyperechogenic kidney). Esophageal atresia (EA) type C was identified at birth in one patient while none had neurological disorder. Because EA has already been identified in patients with 17q12 duplication or HNF1B point mutation, we screened HNF1B (QMPSF and direct sequencing) in nine additional patients with EA and renal abnormalities but failed to identify any pathogenic variant. This is the second report of HNF1B mutation associated with EA. Moreover, we showed herein, that renal malformations may be part of the 17q12 duplication syndrome.
17q12区域（包括HNF1B转录因子）的染色体失衡最近已成为一种常见病症。在患有各种肾脏异常、糖尿病（5型成年发病型糖尿病）、生殖道或肝脏检查异常的患者中发现了17q12缺失，而在一部分患有自闭症、智力障碍、癫痫和/或精神分裂症但无肾脏疾病的患者中发现了17q12重复。我们在此报告了两名携带17q12重复且有各种肾脏异常（双侧发育不全肾伴膀胱输尿管反流或多囊性发育不良肾伴对侧肾回声增强）的一级亲属。一名患者出生时被诊断为C型食管闭锁（EA），而两人均无神经系统疾病。由于在17q12重复或HNF1B点突变的患者中已发现EA，我们对另外9名患有EA和肾脏异常的患者进行了HNF1B筛查（QMPSF和直接测序），但未发现任何致病变异。这是与EA相关的HNF1B突变的第二篇报道。此外，我们在此表明，肾脏畸形可能是17q12重复综合征的一部分。
