This article
reports a case of
limb-girdle muscular dystrophy type 1B (LGMD1B) caused by a novel splicing heterozygous
mutation in the LMNA
gene. The proband presented with progressive
aggravation of weakness in
walking. There was no
atrophy of the scapular
muscles and the lower-
extremity proximal
muscles, with normal
muscle tension of the
extremities, grade 4
muscle strength in the upper and
lower extremities, and positive Gower sign. The level of
creatine kinase was 779 U/L.
Muscle hematoxylin-
eosin staining showed
muscular dystrophy, and there was no significant reduction in the expression of
Lamin A protein. Second-generation sequencing revealed a novel splicing heterozygous
mutation, c.810+2T>C, in the LMNA
gene, while this locus was normal in his
parents. GERP++RS
software predicted that the
mutation site was highly conservative.
Human Splice Finder and Spliceman
software predicted that the
mutation might be a pathogenic
mutation. ExPASy
software predicted that the new
amino acid sequence became shorter. There were two sequences of
mRNA in the
patient's
muscle one was the normal sequence, which accounted for 92.2%; the other was partial
intron 4 retention, which was the abnormal splice variant
accounting for 7.8%. LGMD1B is a type of autosomal dominant inherited
myopathy caused by a
mutation in the LMNA
gene located on the autosomal 1q22. This study extends the
mutation spectrum of the LMNA
gene and provides help to the
diagnosis of LGMD1B.