|
KMID : 0613820210310100913
|
|
Journal of Life Science
2021 Volume.31 No. 10 p.913 ~ p.921
|
|
|
Identification of Compound Heterozygous Alleles in a Patient with Autosomal Recessive Limb-Girdle Muscular Dystrophy
|
|
Choi Hee-Ji
Lee Soo-Bin
Kwon Hye-Mi
Choi Byung-Ok
Chung Ki-Wha
|
|
|
Abstract
|
|
|
|
Limb-girdle muscular dystrophy (LGMD) which is characterized by progressive muscle weakening of the hip and shoulder shows both dominant and recessive inheritances with many pathogenic genes including TTN. This study performed to identify genetic causes of a male patient with late onset (45 years old) autosomal recessive LGMD and atrial flutter. By application of the whole exome sequencing, we identified bi-allelic variants of TTN gene in the patient. One allele had a single missense variant of [c.24124G>T (p.V8042F)], while the other allele consisted of three missense variants of [c.29222G>C (p.R9741P) + c.67490A>G (p.H22497R) + c.75376C>T (p.R25126C)]. The p.V8042F allele was transmitted from his mother, while the other haplotype allele was putatively transmitted from his father. His two unaffected sons had only the p.R9741P. These variants have been not reported or rarely reported in the public human genome databases (1,000 Genome, gnomAD, and KRGDB). Most variants were located in the highly conserved immunoglobulin or fibronectin domains and were predicted to be pathogenic by the in silico analyses. The TTN giant protein plays a key role in muscle assembly, force transmission at the Z-line, and maintenance of resting tension in the I-band. In conclusion, we think that these bi-allelic compound heterozygous mutations may play a role as the genetic causes of the LGMD phenotype.
|
|
|
KEYWORD
|
|
|
Haplotype allele, limb-girdle muscular dystrophy (LGMD), myopathy, TTN, whole exome sequencing
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|