Laffargue Fanny, Bourthoumieu Sylvie, Llanas Brigitte, Baudouin Véronique, Lahoche Annie, Morin Denis, Bessenay Lucie, De Parscau Loïc, Cloarec Sylvie, Delrue Marie-Ange, Taupiac Emmanuelle, Dizier Emilie, Laroche Cécile, Bahans Claire, Yardin Catherine, Lacombe Didier, Guigonis Vincent
Department of Paediatrics, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
Department of Cytogenetic, CHREC, Limoges University Hospital, Limoges, France.
Arch Dis Child. 2015 Mar;100(3):259-64. doi: 10.1136/archdischild-2014-306810. Epub 2014 Oct 16.
17q12 microdeletion syndrome involves 15 genes, including HNF1B, and is considered to confer a high risk of neuropsychiatric disorders. Patients with HNF1B gene deletion diagnosed secondary to renal disorders are only very rarely reported to have neuropsychiatric disorders. Interestingly, however, when tested, patients with HNF1B gene deletion are found to have 17q12 deletion. This brings into question the extent to which 17q12 deletion is genuinely associated with severe neuropsychological disorders and in which patients. In this study, we sought to confirm 17q12 microdeletion in kidney patients initially diagnosed with HNF1B gene deletion and evaluate neuropsychological disorders in these patients compared with those with HNF1B point mutation.
Thirty-nine children with HNF1B disorders (26 with deletions) diagnosed secondary to renal abnormalities were included in this prospective study and tested for 17q12 microdeletion and neuropsychological disorders.
The same 17q12 microdeletion found in patients with neuropsychological disorders was identified in all of our patients with HNF1B deletion. Neurological examinations found no severe impairments except for one patient with autism. No significant differences were found between patients with deletions and those with point mutations as concerns learning abilities and schooling. Nevertheless, patients with deletions tended to have lower developmental quotients and more difficulties at school.
Complete deletion of the HNF1B gene and 17q12 microdeletion syndrome are actually the same genetic disorder. The neuropsychological phenotype of patients appears less severe when 17q12 deletion is diagnosed secondary to kidney rather than neuropsychological abnormalities. These data may influence antenatal counselling.
17q12微缺失综合征涉及15个基因，包括HNF1B，被认为具有较高的神经精神疾病风险。继发于肾脏疾病而被诊断出HNF1B基因缺失的患者仅有极少数被报道患有神经精神疾病。然而，有趣的是，经检测发现，HNF1B基因缺失的患者存在17q12缺失。这使得17q12缺失与严重神经心理障碍真正相关的程度以及涉及哪些患者受到质疑。在本研究中，我们试图在最初被诊断为HNF1B基因缺失的肾脏疾病患者中确认17q12微缺失，并与HNF1B点突变患者相比，评估这些患者的神经心理障碍。
本前瞻性研究纳入了39例继发于肾脏异常而被诊断为HNF1B疾病的儿童（26例为缺失型），并对其进行17q12微缺失和神经心理障碍检测。
我们所有HNF1B缺失的患者均检测出与神经心理障碍患者相同的17q12微缺失。神经学检查发现，除一名自闭症患者外，无严重损伤。在学习能力和学业方面，缺失型患者与点突变患者之间未发现显著差异。然而，缺失型患者的发育商往往较低，在学校遇到的困难更多。
HNF1B基因的完全缺失与17q12微缺失综合征实际上是同一种遗传疾病。当17q12缺失继发于肾脏疾病而非神经心理异常时，患者的神经心理表型似乎不那么严重。这些数据可能会影响产前咨询。
