VARIETY OF CLINICAL MANIFESTATIONS IN MUTATIONS IN THE DYNC1H1 GENE

Introduction. To date, DYNC1H1 gene mutations are known for large number of hereditary diseases. It is believed that different mutations have variable effects to protein function and, accordingly, to various clinical manifestations. Results. There are a clinical and genetic characteristics of two Russian patients with two types of diseases: spinal muscular atrophy with predominant lesion of the lower extremities (SMALED) and non-syndromic mental retardation type 13 (MR13) in combination with a brain malformations and epilepsy due to newly identified mutations in the DYNC1H1 gene. Conclusion There is some evidence in support of the hypothesis that the amino acid sequence changing in the tail domain of dynein lead to the appearance of SMALED, and in the motor domain lead to MR13. Exome or genome sequencing are required as the main method for their diagnosis due to the high genetic heterogeneity of non-syndromic MR and SMALED, the lack of specific clinical markers and hotspot mutations in the DYNC1H1 gene.