VARIETY OF CLINICAL MANIFESTATIONS IN MUTATIONS IN THE DYNC1H1 GENE
https://doi.org/10.30629/2658-7947-2019-24-3-31-36
Abstract
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.
Keywords
spinal muscular atrophy with predominant lesion of the legs,
mental retardation type 13,
dynein,
exome sequencing,
SMALED
Supporting agencies: The study had no sponsorship.
About the Authors
I. V. Sharkova
Research Center of Medical Genetics
Russian Federation
Ph.D., leading researcher in scientific-advisory department
Russian Federation
Ph.D., leading researcher in scientific-advisory department
P. A. Shatalov
LLC «Genotek»
Russian Federation
head of the Departament of Hereditary Diseases Diagnostics
Russian Federation
head of the Departament of Hereditary Diseases Diagnostics
E. L. Dadali
Research Center of Medical Genetics;
Pirogov Russian National Research Medical University
Russian Federation
MD, professor indepartment of Molecular and Cell Genetics of the Medical and Biological Faculty of Pirogov Russian National Research Medical University, head of the scientific advisory departmentof the Research Center of Medical Genetics
Russian Federation
MD, professor indepartment of Molecular and Cell Genetics of the Medical and Biological Faculty of Pirogov Russian National Research Medical University, head of the scientific advisory departmentof the Research Center of Medical Genetics
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Review
For citations:
Sharkova I.V., Shatalov P.A., Dadali E.L. VARIETY OF CLINICAL MANIFESTATIONS IN MUTATIONS IN THE DYNC1H1 GENE. Russian neurological journal. 2019;(3):31-36. (In Russ.) https://doi.org/10.30629/2658-7947-2019-24-3-31-36
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