Babin Patricia L, Rao Sudheendra N R, Chacko Anita, Alvina Fidelia B, Panwala Anil, Panwala Leena, Fumagalli Danielle C
Rare Genomics Institute, Downey, CA, United States.
INADcure Foundation, Fairfield, NJ, United States.
Front Genet. 2018 Dec 10;9:597. doi: 10.3389/fgene.2018.00597. eCollection 2018.
Infantile Neuroaxonal Dystrophy (INAD) is a rare neurodegenerative disease that often cuts short the life span of a child to 10 years. With a typical onset at 6 months of age, INAD is characterized by regression of acquired motor skills, delayed motor coordination and eventual loss of voluntary muscle control. Biallelic mutations in the PLA2G6 gene have been identified as the most frequent cause of INAD. We highlight the salient features of INAD molecular pathology and the progress made in molecular diagnostics. We reiterate that enhanced molecular diagnostic methodologies such as targeted gene panel testing, exome sequencing, and whole genome sequencing can help ascertain a molecular diagnosis. We describe how the defective catalytic activity of the PLA2G6 gene could be potentially overcome by enzyme replacement or gene correction, giving examples and challenges specific to INAD. This is expected to encourage steps toward developing and testing emerging therapies that might alleviate INAD progression and help realize objectives of patient formed organizations such as the INADcure Foundation.
婴儿神经轴索性营养不良（INAD）是一种罕见的神经退行性疾病，常使儿童寿命缩短至10岁。INAD通常在6个月大时发病，其特征是已获得的运动技能退化、运动协调延迟以及最终丧失自主肌肉控制能力。PLA2G6基因的双等位基因突变已被确定为INAD最常见的病因。我们重点介绍了INAD分子病理学的显著特征以及分子诊断方面取得的进展。我们重申，诸如靶向基因panel检测、外显子组测序和全基因组测序等增强型分子诊断方法有助于确定分子诊断。我们描述了如何通过酶替代或基因校正来潜在地克服PLA2G6基因的缺陷催化活性，并给出了特定于INAD的实例和挑战。这有望鼓励采取措施开发和测试可能减轻INAD进展的新兴疗法，并有助于实现诸如INADcure基金会等患者组织的目标。
