Novel DYNC1H1 mutation

Spinal muscular atrophy, lower extremity predominant (SMALED), is a group of non-5q spinal muscular atrophy (SMA) characterized by weakness and atrophy of lower limb muscles without sensory abnormalities. Dynein Cytoplasmic 1 Heavy Chain 1 (DYNC1H1) gene variants can cause SMALED1. Here, we report on a large Chinese family with SMALED1 and a novel mutation in exon 4 of the DYNC1H1 gene (c.587T＞C, p.Leu196Ser). The mutation model analysis showed that Ser196 could strengthen the polar interactions with Gly192, which may contribute to DYNC1H1 protein dysfunction. Combining our patients' genotypes and phenotypes, we demonstrated that SMALED1 was the definite diagnosis.