Rahmani Behrouz, Fekrmandi Fatemeh, Ahadi Keivan, Ahadi Tannaz, Alavi Afagh, Ahmadiani Abolhassan, Asadi Sareh
Section of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
BMC Neurol. 2018 Nov 29;18(1):195. doi: 10.1186/s12883-018-1201-6.
Hereditary sensory and autonomic neuropathy type 2 (HSAN2) is an autosomal recessive disorder with predominant sensory dysfunction and severe complications such as limb destruction. There are different subtypes of HSAN2, including HSAN2A, which is caused by mutations in WNK1/HSN2 gene.
An Iranian family with four siblings and autosomal recessive inheritance pattern whom initially diagnosed with HSAN2 underwent whole exome sequencing (WES) followed by segregation analysis.
According to the filtering criteria of the WES data, a novel candidate variation, c.3718C > A in WNK1/HSN2 gene that causes p.Tyr1025* was identified. This variation results in a truncated protein with 1025 amino acids instead of the wild-type product with 2645 amino acids. Sanger sequencing revealed that the mutation segregates with disease status in the pedigree.
The identified novel nonsense mutation in WNK1/HSN2 in an Iranian HSAN2 pedigree presents allelic heterogeneity of this gene in different populations. The result of current study expands the spectrum of mutations of the HSN2 gene as the genetic background of HSAN2A as well as further supports the hypothesis that HSN2 is a causative gene for HSAN2A. However, it seems that more research is required to determine the exact effects of this product in the nervous system.
2型遗传性感觉和自主神经病变（HSAN2）是一种常染色体隐性疾病，主要表现为感觉功能障碍以及诸如肢体损毁等严重并发症。HSAN2有不同的亚型，包括由WNK1/HSN2基因突变引起的HSAN2A。
一个有四名兄弟姐妹且呈常染色体隐性遗传模式的伊朗家庭，最初被诊断为HSAN2，随后进行了全外显子组测序（WES），接着进行了分离分析。
根据WES数据的筛选标准，在WNK1/HSN2基因中鉴定出一个新的候选变异，即c.3718C＞A，该变异导致p.Tyr1025*。此变异产生一种截短的含有1025个氨基酸的蛋白质，而非野生型的含有2645个氨基酸的产物。桑格测序显示该突变在系谱中与疾病状态共分离。
在一个伊朗HSAN2系谱中WNK1/HSN2基因鉴定出的新无义突变呈现出该基因在不同人群中的等位基因异质性。当前研究结果扩展了作为HSAN2A遗传背景的HSN2基因突变谱，同时进一步支持了HSN2是HSAN2A致病基因的假说。然而，似乎需要更多研究来确定该产物在神经系统中的确切作用。
