Study of Muscular Dystrophy (TTN Gene) in One Family from Khuzestan Using Whole Exome Sequencing

Abstract

Background: Tibial muscular dystrophy (TMD) is a type of muscle disease primarily affecting the lower legs. It typically begins in adulthood and is inherited through families in a dominant pattern, meaning that only one copy of the affected gene is required to pass the condition. It is associated with mutations in the TTN gene, located on chromosome 2q31, responsible for encoding the central sarcomeric protein titin. The TTN gene is a very large gene with 363 coding sections (exons). It provides instructions for making a huge protein called titin, which stretches across the sarcomere — the basic unit of muscle — from the Z disc to the M band. Changes (mutations) in the TTN gene can cause a variety of inherited conditions, including heart problems such as hypertrophic and dilated cardiomyopathy, as well as several muscle-related disorders. Methods: In this study, after collecting the patients' and parents' peripheral blood, DNA extraction was done using the salting-out method, and the sample was sequenced to check the exons. Results: Findings confirm the existence of the mutation NM_1333793 c.14952_14960 del (p.Leu4984_Gln4986del), which is heterozygous in the patient. Sequencing of the mother's genome also confirms this mutation. Conclusions: The results of this research show that due to the uncontrollable consequences of this mutation, the new whole exome sequencing (WES) method can be effective for screening before birth and marriage and reduce the psychological and treatment burden of such diseases in society.