Heterozygous missense variant in the TTN gene causing Tibial muscular dystrophy

Abstract

Background Tibial muscular dystrophy (TMD), tardive, is a dominantly inherited mild degenerative disorder of anterior tibial muscles. Mutations of Titin (TTN) have been reported in patients with different phenotypes such as skeletal muscular abnormalities or complex overlapping disorders of muscles. Titin (TTN) is a large 363 exon gene that encodes an abundant protein (the longest polypeptide known in nature) expressed in the heart and skeletal muscles. Methods DNA from peripheral blood sample was extracted, whole exome sequencing (WES) was performed, and a neuromuscular disorders related gene-filtering strategy was used to analyse the disease-causing mutations. Further, sanger sequencing was applied to confirm the variant. Results A novel missense variant (c.41529G > C;p.Arg13843Ser) of TTN gene was identified in a patient with lower limb weakness, occasional tongue fasciculation and mild scoliosis. This variant leads to a substitution of arginine with serine, causing structural changes in titin protein that is responsible for the TMD disease. Conclusion The novel variant detected has widened the genetic spectrum of TTN-associated diseases, further functional studies will aid in establishing the clinical diagnosis.