Abstract：
Inherited peripheral neuropathy (IPN) is a heterogeneous group of disorders due to pathogenic variation in more than 100 genes. In 2012, the first cases of IPN associated with HINT1 pathogenic variations were described in 33 families sharing the same phenotype characterized by an axonal neuropathy with neuromyotonia and autosomal recessive inheritance (NMAN: OMIM #137200). Histidine Triad Nucleotide Binding Protein 1 regulates transcription, cell-cycle control, and is possibly involved in neuropsychiatric pathophysiology. Herein, we report seven French patients with NMAN identified by Next Generation Sequencing. We conducted a literature review and compared phenotypic and genotypic features with our cohort. We identified a new HINT1 pathogenic variation involved in NMAN: c.310G>C p.(Gly104Arg). This cohort is comparable with literature data regarding age of onset (7,4yo), neuronal involvement (sensorimotor 3/7 and motor pure 4/7), and skeletal abnormalities (scoliosis 3/7, feet anomalies 6/7). We expand the phenotypic spectrum of HINT1-related neuropathy by describing neurodevelopmental or psychiatric features in six out of seven individuals such as generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), mood disorder and attention deficit hyperactivity disorder (ADHD). However, only 3/128 previously described patients had neuropsychiatric symptomatology or neurodevelopmental disorder. These features could be part of HINT1-related disease, and we should further study the clinical phenotype of the patients.
摘要：
遗传性周围神经病变（IPN）是由于100多个基因的致病变异而引起的一组异质性疾病。2012年，在33个具有相同表型的家庭中描述了与HINT1致病性变异相关的IPN首例，其特征是轴索性神经病伴神经肌强直和常染色体隐性遗传（NMAN：OMIM＃137200）。组氨酸三联体核苷酸结合蛋白1调节转录，细胞周期控制，并可能参与神经精神病理生理学。在这里，我们报告了通过下一代测序确定的7名法国NMAN患者。我们进行了文献综述，并将表型和基因型特征与我们的队列进行了比较。我们确定了一个新的HINT1致病变异涉及NMAN：c.310G>Cp。（Gly104Arg）。该队列与有关发病年龄（7,4yo）的文献数据具有可比性，神经元受累（感觉运动3/7和纯运动4/7），和骨骼异常（脊柱侧凸3/7，脚异常6/7）。我们通过描述七个个体中的六个个体的神经发育或精神病学特征，如广泛性焦虑症（GAD），扩大了HINT1相关神经病的表型谱。强迫症（强迫症），心境障碍和注意缺陷多动障碍（ADHD）。然而,只有3/128以前描述过的患者有神经精神症状或神经发育障碍.这些特征可能是HINT1相关疾病的一部分，我们应该进一步研究患者的临床表型。
