A Pathogenic Missense Variant (c.1617G>A, p.Met539Ile) in Causing Infantile X-Linked Spinal Muscular Atrophy (SMAX2).

Infantile X-linked spinal muscular atrophy (SMAX2) is a rare type of spinal muscular atrophy associated with variants. Clinical imaging and neurophysiological tests were performed on a Chinese patient with SMAX2. Further, focused panel sequencing of was carried out on samples of both the proband and his maternal relatives. The proband, a 4-year-old boy with the SMAX2 phenotype, suffered from reduced exercise capacity since infancy. His other symptoms included speech difficulties, severe nasal tone, reduced distal muscle strength, areflexia, and inadequate sucking ability. The brain MRI of the proband's showed normal results but the electromyography results showed multiple peripheral neurogenic lesions. Five male members of the proband's family were affected with the SMAX2 phenotype. They presented similar symptoms and had experienced a long and autonomous life. Molecular analysis revealed a novel missense variant (c.1617G>A, p.Met539Ile) in the exon 15 of . The proband's mother, as well as grandmother, carried the heterozygous missense variant; whereas, the male patients from the family carried the hemizygotic variant. The affected members in this Chinese family showed unique features such as extended life span, no fractures, and cramps as compared with previously reported SMAX2 cases. The novel missense variant (c.1617G>A (p.Met539Ile) in UBA1 highlights the critical role of this gene in causing SMAX2 phenotype.