{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T15:46:45Z","timestamp":1763480805437,"version":"3.33.0"},"reference-count":31,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Introduction\u2003The Alsin Rho Guanine Nucleotide Exchange Factor (ALS2) gene encodes a protein alsin that functions as a guanine nucleotide exchange factor. The variations in ALS2 gene leads to degeneration of upper motor neurons of the corticospinal tract. The phenotypes resulting from variants in ALS2 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 ALS2 gene-related disorder.<\/jats:p><jats:p>\n          Methods\u2003The clinical details, laboratory data, and genotype findings of children with an established diagnosis of ALS2 gene-related disorder were collected from the hospital electronic database after obtaining institutional review board approval.<\/jats:p><jats:p>\n          Results\u2003One family with three affected siblings, a second family with a proband and an affected fetus, and a third family with two affected siblings with ALS2 gene variants were identified. IAHSP was diagnosed in all of our patients with variants in ALS2 gene. The clinical findings observed in our patients were insidious onset progressive spastic paraparesis, contractures, and dysarthria. Nonsense variants\t were observed in four patients while frameshift variant was observed in one family. Novel variants in ALS2 gene were identified in two unrelated families.<\/jats:p><jats:p>\n          Conclusion\u2003ALS2 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\u2013phenotype correlation in patients with ALS2 gene-related disorder.<\/jats:p>","DOI":"10.1055\/s-0044-1791256","type":"journal-article","created":{"date-parts":[[2024,10,19]],"date-time":"2024-10-19T01:03:33Z","timestamp":1729299813000},"page":"020-028","source":"Crossref","is-referenced-by-count":2,"title":["Phenotype and Genotype of Children with ALS2 gene-Related Disorder"],"prefix":"10.1055","volume":"56","author":[{"given":"Sangeetha","family":"Yoganathan","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Neurological Sciences, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhan","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rekha","family":"Aaron","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srinivasa Raghavan","family":"Rangan","sequence":"additional","affiliation":[{"name":"Developmental Pediatrics Unit, Department of Pediatrics, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bidkar Sayli","family":"Umakant","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Neurological Sciences, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maya","family":"Thomas","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Neurological Sciences, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel Philip","family":"Oommen","sequence":"additional","affiliation":[{"name":"Developmental Pediatrics Unit, Department of Pediatrics, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumita","family":"Danda","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/brain\/113.2.347","article-title":"Hereditary motor system diseases (chronic juvenile amyotrophic lateral sclerosis). 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