Yoganathan Sangeetha, Kumar Madhan, Aaron Rekha, Rangan Srinivasa Raghavan, Umakant Bidkar Sayli, Thomas Maya, Oommen Samuel Philip, Danda Sumita
Pediatric Neurology Unit, Department of Neurological Sciences, Christian Medical College, Vellore, Tamil Nadu, India.
Department of Pediatrics, Christian Medical College, Vellore, Tamil Nadu, India.
Neuropediatrics. 2025 Feb;56(1):20-28. doi: 10.1055/s-0044-1791256. Epub 2024 Oct 18.
The Alsin Rho Guanine Nucleotide Exchange Factor ( gene encodes a protein alsin that functions as a guanine nucleotide exchange factor. The variations in gene leads to degeneration of upper motor neurons of the corticospinal tract. The phenotypes resulting from variants in gene are infantile-onset ascending hereditary spastic paralysis (IAHSP, OMIM # 607225), juvenile primary lateral sclerosis (JPLS, OMIM # 606353), and juvenile amyotrophic lateral sclerosis (JALS, OMIM # 205100). Our study objectives were to describe the clinical phenotype and genotype of children with an established diagnosis of gene-related disorder.
The clinical details, laboratory data, and genotype findings of children with an established diagnosis of gene-related disorder were collected from the hospital electronic database after obtaining institutional review board approval.
One family with three affected siblings, a second family with a proband and an affected fetus, and a third family with two affected siblings with gene variants were identified. IAHSP was diagnosed in all of our patients with variants in gene. The clinical findings observed in our patients were insidious onset progressive spastic paraparesis, contractures, and dysarthria. Nonsense variants were observed in four patients while frameshift variant was observed in one family. Novel variants in gene were identified in two unrelated families.
mutation results in rare neurodegenerative disorders with the clinical spectrum encompassing IAHSP, JPLS, and JALS disorders. In view of allelic heterogeneity described in the literature, more research studies are needed for establishing genotype-phenotype correlation in patients with gene-related disorder.
阿尔辛Rho鸟嘌呤核苷酸交换因子（基因编码一种名为阿尔辛的蛋白质，其作为鸟嘌呤核苷酸交换因子发挥作用。该基因的变异会导致皮质脊髓束的上运动神经元退化。该基因变异导致的表型有婴儿期起病的进行性遗传性痉挛性截瘫（IAHSP，OMIM # 607225）、青少年原发性侧索硬化症（JPLS，OMIM # 606353）和青少年肌萎缩侧索硬化症（JALS，OMIM # 205100）。我们的研究目的是描述已确诊患有该基因相关疾病的儿童的临床表型和基因型。
在获得机构审查委员会批准后，从医院电子数据库中收集已确诊患有该基因相关疾病的儿童的临床细节、实验室数据和基因型结果。
确定了一个有三个患病兄弟姐妹的家庭、一个有先证者和一个患病胎儿的家庭以及一个有两个携带该基因变异的患病兄弟姐妹的家庭。我们所有携带该基因变异的患者均被诊断为IAHSP。我们的患者观察到的临床发现为隐匿性起病的进行性痉挛性截瘫、挛缩和构音障碍。四名患者观察到无义变异，而在一个家庭中观察到移码变异。在两个无关家庭中鉴定出该基因的新变异。
该基因突变导致罕见的神经退行性疾病，临床谱包括IAHSP、JPLS和JALS疾病。鉴于文献中描述的等位基因异质性，需要更多的研究来建立该基因相关疾病患者的基因型 - 表型相关性。
