Section of Neurology, Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA.
Am J Med Genet A. 2010 May;152A(5):1300-4. doi: 10.1002/ajmg.a.33374.
We identified a novel homozygous 15q13.3 microdeletion in a young boy with a complex neurodevelopmental disorder characterized by severe visual impairment, hypotonia, profound intellectual disability, and refractory epilepsy. The homozygous deletion of the genes within this deleted region provides a useful insight into the pathogenesis of the observed clinical phenotype. Absence of the Transient Receptor Potential Cation Channel, Subfamily M, Member 1 (TRPM1) gene product is proposed as a possible mechanism for the severe visual impairment; absence of CHRNA7 (alpha7-nicotinic receptor subunit) as a cause of the refractory seizures and severe cognitive impairment; and deletion of MTMR10 and/or MTMR15 (encoding myotubularin related proteins) alone or combined with other homozygously deleted genes as a cause for the congenital hypotonia with areflexia. The distinctive clinical findings in this patient reveal potential functions of the genes within the deleted region.
我们在一名患有复杂神经发育障碍的年轻男孩中鉴定出一个新的 15q13.3 纯合性微缺失，该疾病的特征为严重的视力障碍、肌张力低下、严重的智力障碍和难治性癫痫。该缺失区域内基因的纯合性缺失为观察到的临床表型的发病机制提供了有用的见解。TRPM1 基因产物的缺失被认为是严重视力障碍的可能机制；CHRNA7（α7-烟碱型受体亚单位）的缺失是难治性癫痫和严重认知障碍的原因；而 MTMR10 和/或 MTMR15（编码肌管相关蛋白）的缺失，单独或与其他纯合性缺失基因一起，可能导致先天性肌张力低下和反射消失。该患者的独特临床发现揭示了缺失区域内基因的潜在功能。
