Hosseini Bereshneh Ali, Hosseipour Sareh, Rasoulinezhad Maryam Sadat, Pak Neda, Garshasbi Masoud, Tavasoli Ali Reza
Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Myelin Disorders Clinic, Pediatric Neurology Division, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
Eur J Med Genet. 2020 May;63(5):103868. doi: 10.1016/j.ejmg.2020.103868. Epub 2020 Jan 28.
Pathogenic variants in NKX6-2 gene causing autosomal recessive spastic ataxia type 8 with hypomyelinating leukodystrophy have been reported in few families around the world. In this study, we performed Whole Exome Sequencing and identified a novel missense variant, c.501C > G; p.(Phe167Leu), in two affected siblings with main manifestations of global developmental delay, motor regression, hypotonia, clonus in lower limbs and muscle bulk atrophy especially in the upper limbs, spasticity and contracture, scoliosis, hip dislocation, oculomotor apraxia, horizontal and vertical nystagmus. In addition, wrist and foot drop due to peripheral axonal neuropathy were observed in these patients as a new clinical finding and cerebellar white matter involvement in brain Magnetic Resonance Imaging (MRI) as new imaging finding. Therefore, we expanded the manifestations of NKX6-2-related disorders in this manuscript.
世界各地少数家庭报告了NKX6-2基因的致病变异，其导致常染色体隐性遗传性8型痉挛性共济失调伴低髓鞘性脑白质营养不良。在本研究中，我们对两名受影响的兄弟姐妹进行了全外显子组测序，并鉴定出一种新的错义变异，即c.501C>G；p.(Phe167Leu)，这两名患者的主要表现为全面发育迟缓、运动功能倒退、肌张力减退、下肢阵挛以及尤其是上肢的肌肉萎缩、痉挛和挛缩、脊柱侧弯、髋关节脱位、眼球运动失用、水平和垂直眼球震颤。此外，在这些患者中观察到因周围轴索性神经病变导致的垂腕和垂足，这是一项新的临床发现，并且在脑部磁共振成像（MRI）中发现小脑白质受累，这是一项新的影像学发现。因此，我们在本论文中扩展了NKX6-2相关疾病的临床表现。
