Spectrum of DYNC1H1 mutations in neuromuscular diseases
Previous publications were searched to further investigate the clinical and genetic spectrum of neuromuscular diseases caused by DYNC1H1mutations. A total of 22 original articles out of 49 publications met the inclusion criteria and were included in our study (Fig.S1). These articles identified 39 variants in DYNC1H1 related to neuromuscular diseases. Of the 105 patients, SMA-LED (77, 73.3%) and CMT2O (16, 15.2%) accounted for the most part. Among the SMA-LED patients, two were initially diagnosed with polio and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), respectively. Other types of neuromuscular diseases, such as hereditary spastic paraplegia (HSP), were also reported caused by DYNC1H1 variants. All variants were missense mutations, except for one splicing mutation (c.12685-3C>T). One hundred five patients from 58 pedigrees were included, among which all carried one heterozygous variant inDYNC1H1 , except for two patients from a Chinese family harbouring two variants in DYNC1H1 , including c.2419G>A/p.G807S and c.12685-3C>T. Of all the 58 families from all over the world, most were European families (34/58, 58.6%), followed by East Asian (9/58, 15.5%), North American (8/58, 13.8%), Australian (5/58, 8.6%) and Middle East (2/58, 3.4%).